Total synthesis and biological evaluation of glycolipids plakosides A, B, and their analogs

Article abstract of DOI:10.1002/1522-2675(20000809)83:8<1977::AID-HLCA1977>3.0.CO;2-D

The total synthesis of plakosides A (1) and B (2), and their designed analogs 3-10 was accomplished. The convergent strategy employed involved construction of the individual building blocks employing the Sharpless asymmetric dihydroxylation and the Charette asymmetric cyclopropanation reactions to introduce the desired configuration, followed by their couplings and final elaboration. Thus, key intermediates 12-14 were prepared in their optically active forms and joined through a glycosidation reaction and amide-bond formation to yield the target molecules after appropriate elaboration and final deprotection. The synthesized compounds 1-10 were evaluated for their immunosuppressive properties in vitro and found to be only modestly active.

Full text of DOI:10.1002/1522-2675(20000809)83:8<1977::AID-HLCA1977>3.0.CO;2-D

Helvetica Chimica Acta ± Vol. 83 (2000)
1977
Total Synthesis and Biological Evaluation of Glycolipids Plakosides A, B
and Their Analogs
by Kyriacos C. Nicolaoua)*, Jim Lia), and Gerhard Zenkeb)
a) Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute,
10550 North Torrey Pines Road, La Jolla, California 92037, USA, and Department of Chemistry and
Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
b) Novartis Pharma AG, Transplantation Research, WSJ-386.127, CH-4002, Basel
Dedicated to Professor Albert Eschenmoser on the occasion of his 75th birthday for his outstanding
contributions to organic and bioorganic chemistry
The total synthesis of plakosides A (1) and B (2), and their designed analogs 3 ± 10 was accomplished. The
convergent strategy employed involved construction of the individual building blocks employing the Sharpless
asymmetric dihydroxylation and the Charette asymmetric cyclopropanation reactions to introduce the desired
configuration, followed by their couplings and final elaboration. Thus, key intermediates 12 ± 14 were prepared
in their optically active forms and joined through a glycosidation reaction and amide-bond formation to yield
the target molecules after appropriate elaboration and final deprotection. The synthesized compounds 1 ± 10
were evaluated for their immunosuppressive properties in vitro and found to be only modestly active.
Introduction. ± Plakosides A and B (1 and 2, Fig. 1) are two naturally occurring
glycosphingolipids (GSLs) whose structures and biological properties have recently
been reported [1]. Isolated from the marine sponge Plakortis simplex, these
glycosphingolipids are novel among many members of their class, since they are the
first found to include a cyclopropane ring in their sphingosine chain and a prenylated 2-
O-substituent on their carbohydrate moiety. Interestingly, the latter functionality has
been associated with the immunosuppressive properties exhibited by these compounds
[1 ± 3]. The potent immunosuppressive activity reported for plakosides A (1) and B (2)
stands in contrast to other related glycosphingolipids, which are either inactive or
immunostimulating [4 ± 6]. To further investigate the biological properties of these new,
but scarce, natural products, we initiated a program aimed at their total synthesis and
the synthesis of selective analogs. In this article, we describe an efficient and
stereocontrolled total synthesis that delivers not only plakosides A (1) and B (2), but
also their analogs 3 ± 10 (Fig. 1), as well as their biological evaluation as potential
immunosuppressive agents.
Results and Discussion. ± Retrosynthetic Analysis. The structures of plakosides A
(1) and B (2) render themselves to the obvious retrosynthetic disconnections shown in
Fig. 2. The disassembly at the strategic glycosidic, amide, and prenyl ether bonds reveal
primary alcohols 13 (plakoside A) or 14 (plakoside B), galactosyl fluoride 11, and
prenyl bromide (1-bromo-3-methylbut-2-ene; 15) as the key building blocks required
for the total synthesis. It was envisioned that the absolute configuration of the

1978
Helvetica Chimica Acta ± Vol. 83 (2000)
Fig. 1. Structures of plakosides A (1), B (2) and their analogs 3 ± 10
cyclopropane rings would arise from a Charette cyclopropanation [7]. The O-bearing
stereogenic centers of the side chains would be generated by two Sharpless asymmetric
dihydroxylation (AD) processes [8]. Selective conversion of the syn-diol resulting from
the latter reaction into the hydroxy azide would then produce a precursor to the
required amino-alcohol moiety on the sphingosine chain. The installation of a pivaloate
group at the 2-O on the galactosyl fluoride was the designed element by which we were
hoping to direct the glycosidation reaction in the desired sense (b-configuration) [9± 11].
The two-stage activation procedure [10] for the glycosidation step was reserved for the
key coupling of the galactose moiety with the azide-containing sphingosine equivalent.
Synthesis of Galactosyl Fluoride 11. Galactosyl fluoride 11 was obtained from
commercially available galactose pentaacetate 16 in six steps as shown in Scheme 1. The
exposure of 16 to thiophenol in the presence of a catalytic amount of SnCl4 provided
thiogalactoside 17 in excellent yield and selectivity (94%, b/a > 15 :1). Chromato-
graphically purified b-thiogalactoside 17 was exposed to a catalytic amount of MeONa
in MeOH to provide tetraol 18, which was selectively monosilylated at the primary
position (TBDPSCl and imidazole in DMF; for abbreviations of reagents and
protecting groups, see legends in the Schemes) to afford triol 19 in 97% overall yield
from 17. Engagement of the 3,4-diol system of 19 as an acetonide was accomplished by
treatment with 2,2-dimethoxypropane in the presence of CSA to furnish compound 20
(89% yield). The remaining OH group was reacted with pivaloyl chloride and
4-DMAP in refluxing pyridine to give pivaloate ester 21 in 99% yield. Finally, exposure
of 21 to DAST in the presence of the activator DMTST led to the desired galactosyl
fluoride 11 in 94% yield and a ca. 11:1 ratio of b/a-anomers [12]. This mixture was
directly used for the glycosidation step without further separation.

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Fig. 2. Retrosynthetic analysis of plakosides A (1) and B (2). Piv ˆ pivaloyl; TBDMS ˆ (t-Bu)Me2Si; TBDPS ˆ
(t-Bu)Ph2Si.
Synthesis of Azides 13 and 14. Employing the Sharpless [8] and Charette [7]
methodologies, enantioselective syntheses of the requisite azides 13 (Scheme 2) and 14
(Scheme 3) were developed. Starting from commercially available tridec-2-yn-1-ol
(22), the (Z)-alcohol 23 was obtained in 96% yield by selective hydrogenation (H2, 5%
Pd on BaSO4) [13]. Charette asymmetric cyclopropanation [7] of 23 using bis(iodo-
methyl)zinc ´ DME complex and (R,R)-dioxaborolane 24 resulted in the formation of
25 in 96% yield and 84% ee1). Exposure of alcohol 25 to Ph3P and I2 in the presence of
1
)
The ee value [%] was determined from comparison of [a]D values of cyclopropanemethanol 25 prepared as
shown in Scheme 2 and the following procedure. From known (‡)-(1S,2R)-2-(benzyloxymethyl)cyclo-
propanemethanol (93% ee) [7b], conversion of the alcohol to the iodide and followed by coupling with
Grignard reagent from 1-bromononane in the presence of Li2CuCl4 catalyst, and finally removal of the
PhCH2 group afforded 25.

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Scheme 1. Synthesis of Galactosyl Fluoride 11
a) PhSH (1.2 equiv.), SnCl4 (0.1 equiv.), CH2Cl2, À158, 3.5 h; 94%. b) MeONa (0.2 equiv.), MeOH, 258, 1 h. c)
TBDPSCl (1.3 equiv.), imidazole (1.3 equiv.), DMF, 08, 1.5 h; 97% for 2 steps. d) 2,2-Dimethoxypropane
(2.0equiv.), CSA (0.1 equiv.), 25 8, 8 h; 89%. e) PivCl (2.0 equiv.), 4-DMAP (0.05 equiv.), pyridine, reflux, 2 h;
99%. f) DMTST (1.2 equiv.), DAST (3.0equiv.), CH 2Cl2, 0 ! 258, 3 h; 94% (a/b ca. 1:11). Abbreviations:
Ac ˆ acetyl, DASTˆ (diethylamino)sulfur trifluoride, DMF ˆ N,N-dimethylformamide, 4-DMAP ˆ 4-(dime-
thylamino)pyridine, DMTSTˆ dimethyl(methylthio)sulfonium triflate, Piv ˆ pivaloyl, TBDPS ˆ (t-Bu)Ph2Si.
imidazole furnished the corresponding iodo derivative 26 in 96% yield, which was
cross-coupled with the Grignard reagent 27, derived from the THP ether of 7-
bromoheptan-1-ol in the presence of Li2CuCl4 catalyst, to afford product 28 in 87%
yield [14]. Aldehyde 30 was then derived from acidic cleavage of the THP ether from
28 (PPTS, 98% yield), followed by Swern oxidation [15] (96% yield) of the resulting
primary alcohol 29. Olefination of aldehyde 30 ((EtO2P(O)CH2CO2Et, NaH) led to
the a,b-unsaturated ester 31 (94% yield, (E)/(Z) > 95 :5). Asymmetric dihydroxyla-
tion (AD) of 31 with AD mix-b in the presence of MeSO2NH2 proceeded smoothly to
afford the syn-dihydroxy ester 32 in 96% isolated yield [8b]. Selective nosylation [16]
(nosyl (4-nitrobenzenesulfonyl) chloride, pyridine) of the a-OH group of the latter
compound gave nosylate 33 in 90% yield. Displacement of the nosylate group in 33
with azide [16] (NaN3, DMF, 258) then led smoothly to the a-azido-b-hydroxy ester 34
(94% yield), which was silylated (TBDMSOTf, 2,6-lutidine) to afford silyl ether 35 in
quantitative yield. Finally, reduction of the ester group in 35 with LiBH4 in THF at 08
furnished the desired primary alcohol 13 in 95% yield.
The construction of the a-azidosphingosine 14 required for the synthesis of
plakoside B (2) is summarized in Scheme 3. The strategy involved introduction of the

Helvetica Chimica Acta ± Vol. 83 (2000)
Scheme 2. Synthesis of Azidosphingosine 13
1981
a) Pd/BaSO4 (10% w/w), H2 (1 atm), pyridine, 258, 10h; 96%. b) Zn(CH2I)2 ´ DME (3.0equiv.), dioxaborolane
(24) (1.2 equiv.), 4-Š molecular sieves, CH2Cl2, À15 ! 258, 6 h; 96%. c) I2 (1.5 equiv.), Ph3P (1.3 equiv.),
imidazole (1.4 equiv.), Et2O/MeCN 5 :3 (v/v), 08, 1 h; 96%. d) Li2CuCl4 (0.006 equiv.),
BrMgCH2(CH2)5CH2OTHP (27) (1.3 equiv.), THF, 08, 30min; 87%. e) PPTS (0.2 equiv.), MeOH, 558, 4 h;
98%. f) DMSO (2.0equiv.), (COCl) 2 (1.5 equiv.), Et3N (5.0equiv.), CH 2Cl2, À78 ! 258, 1 h, 96%. g)
(EtO)2P(O)CH2CO2Et (1.5 equiv.), NaH (1.5 equiv.), THF, 08, 45 min; 94% ((E)/(Z) > 95 :5). h) AD-mix b
(1.4 g/mmol), MeSO2NH2 (1.0equiv.), t-BuOH/H2O 1:1 (v/v), 08, 8 h; 96%. i) Nos-Cl (1.15 equiv.), pyridine,
08, 7.5 h; 90%. j) NaN3(6.0equiv.), DMF, 25 8, 36 h; 94%. k) TBDMSOTf (1.05 equiv.), 2,6-lutidine (2.5 equiv.),
CH2Cl2, À78 ! 258, 30 min; 100%. l) LiBH4 (2.5 equiv.), THF, 08, 3.5 h; 95%. Abbreviations: AD-mix b ˆ
reagent for Sharpless AD containing (DHQD)2PHAL ligand, DME ˆ dimethoxyethane, DMF ˆ N,N-
dimethylformamide, DMSO ˆ dimethyl sulfoxide, PPTS ˆ pyridinium 4-toluenesulfonate, THP ˆ tetrahydro-
2H-pyran-2-yl, Nos ˆ 4-nitrobenzenesulfonyl, TBDMS ˆ (t-Bu)Me2Si.

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Scheme 3. Synthesis of Azidosphingosine 14
a) Li2CuCl4 (0.006 equiv.), THF, 08, 30min; 84%. b) PPTS (0.2 equiv.), MeOH, 558, 4 h; 100%. c) DMSO
(2.0equiv.), (COCl) 2 (1.5 equiv.), Et3N (5.0equiv.), CH 2Cl2, À78 ! 258, 1 h; 97%. d) CH2PPh3Br (1.6 equiv.),
NaHMDS (1.4 equiv.), THF, 08, 1 h; 97%. e) 9-BBN (1.1 equiv.), H2O2 (1.1 equiv.), NaHCO3, THF, 0 ! 258;
84%. f) DMSO (2.0equiv.), (COCl) 2 (1.5 equiv.), Et3N (5.0equiv.), CH 2Cl2, À78 ! 258, 1 h; 97%. g)
(EtO)2P(O)CH2CO2Et (1.5 equiv.), NaH (1.5 equiv.), THF, 08, 30min; 96% (( E)/(Z) > 98 :2). h) AD-mix b
(1.4 g/mmol), MeSO2NH2 (1.0equiv.), t-BuOH/H2O 1:1 (v/v), 08, 8 h; 97%. j) Lindlar cat. (10% w/w), H2
(1 atm), EtOH, 258, 40 min; 100%. k) Nos-Cl (1.15 equiv.), pyridine, 08, 6.5 h; 84%. l) NaN3 (2.0equiv.), DMF,
258, 36 h; 95%. m) TBDMSOTf (1.05 equiv.), 2,6-lutidine (2.5 equiv.), CH2Cl2, À78 ! 258, 30 min; 100%. n)
LiBH4 (2.5 equiv.), THF, 08, 10h; 92%. Abbreviations: AD-mix b ˆ reagent for Sharpless AD containing
(DHQD)2PHAL ligand, 9-BBN ˆ 9-borabicyclo[3.3.1]nonane, DME ˆ dimethoxyethane, DMF ˆ N,N-dime-
thylformamide, DMSO ˆ dimethyl sulfoxide, NaHMDS ˆ sodium bis(trimethylsilyl)amide, PPTS ˆ pyridinium
4-toluenesulfonate, THP ˆ tetrahydro-2H-pyran-2-yl, Nos ˆ 4-nitrobenzenesulfonyl, TBDMS ˆ (t-Bu)Me2Si.
(Z)-olefin, masked as an acetylenic linkage, after the asymmetric dihydroxylation
(43 ! 44), at which stage Lindlar [17] hydrogenation generated compound 45. The
Grignard reagent 36 was derived from the corresponding bromide (generated from the
THP ether of pent-4-yn-1-ol and 1,3-dibromopropane) [18] and was coupled with
iodide 26 in the presence of Li2CuCl4 catalyst to afford alkyne 37 (84% yield). Removal

Helvetica Chimica Acta ± Vol. 83 (2000)
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of the THP group from 37 (PPTS, 100% yield), followed by Swern oxidation (97%
yield), led to aldehyde 39 via alcohol 38.
The required C1 homologation of aldehyde 39 was accomplished by a Wittig
olefination (CH2ˆPPh3, 40, 97% yield), followed by regioselective hydroboration [19]
(9-BBN, 41, 84% yield). Swern oxidation of the resulting primary alcohol 41 furnished
aldehyde 42 (97% yield). Olefination of 42 with (EtO)2P(O)CH2CO2Et and NaH gave
the a,b-unsaturated ester 43 in 96% yield ((E)/(Z) ca. 98 :2). Asymmetric dihydrox-
ylation of 43 with AD-mix b and MeSO2NH2 gave the syn-dihydroxy ester 44 (97%
yield), which was selectively and quantitatively hydrogenated (H2, Lindlar catalyst) to
afford 45. Selective nosylation of 45 (nosyl chloride, pyridine, 46, 84% yield), followed
by reaction with NaN3 in DMF, furnished azide 47 (95% yield), from which silyl ether
48 was generated quantitatively (TBDMSOTf, 2,6-lutidine). The targeted a-azido-b-
(silyloxy)sphingosine 14 was then obtained in 92% yield by LiBH4 reduction of 48.
Synthesis of a-Hydroxy Carboxylic Acid 12. The construction of the remaining
fragment, a-hydroxy acid 12, proceeded as shown in Scheme 4. Thus, asymmetric
dihydroxylation of the intermediate 40 with ((DHQD)2AQN, K2Os2(OH)4,
K2Fe(CN)6, and K2CO3) resulted in the formation of diol 49 in 91% yield [26].
Selective pivaloate formation proceeded smoothly with 49 in the presence of
stoichiometric amounts of freshly distilled PivCl in pyridine at 08, leading to 50 (91%
yield) [21]. The secondary OH group in 50 was silylated (TBDMSOTf, 2,6-lutidine, 51,
100% yield), and the pivaloate group was cleaved by treatment with DIBAL,
Scheme 4. Synthesis of a-Hydroxy Acid 12
a) (DHQD)2AQN (0.01 equiv.), K2Fe(CN)6 (3.0equiv.), K 2Os2(OH)4 (0.004 equiv.), K2CO3 (3.0equiv.),
t-BuOH/H2O 1:1 (v/v), 08, 8 h; 91%. b) PivCl (1.0equiv.), pyridine, 0 8, 40min; 91%. c) TBDMSOTf
(1.01 equiv.), 2,6-lutidine (2.5 equiv.), CH2Cl2, À78 ! 258, 30 min; 100%. d) DIBAL (2.0equiv.), CH 2Cl2,
À788, 20 min; 100%. e) Lindlar cat. (0.1 equiv.), H2 (1 atm), EtOH, 258, 30 min; 100%. f) Dess-Martin
periodinane (1.2 equiv.), CH2Cl2, 0 ! 258, 40min; 96%. g) NaClO2 (2.5 equiv.), NaH2PO4(12.0equiv.), 2-
methylbut-2-ene (20.0 equiv.), t-BuOH/H2O 5 :1 (v/v), 08, 30min; >95%. Abbreviations: AD-mix b ˆ reagent
for Sharpless AD, in this case containing 1,4-bis(dihydroquinidinyl)anthraquinone ((DHQD)2AQN) ligand,
DIBAL ˆ diisobutylaluminium hydride, Piv ˆ pivaloyl, TBDMS ˆ (t-Bu)Me2Si.

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furnishing primary alcohol 52 in quantitative yield from compound 51. The CꢀC bond
in 52 was then selectively reduced with H2 and Lindlar catalyst to afford the (Z)-olefin
53 in quantitative yield. Finally, stepwise oxidation of 53 furnished first aldehyde 54
(Dess-Martin periodinane, 96% yield) [22] and then the desired hydroxy carboxylic
acid 12 (NaClO2, >95%) [23].
Synthesis of Plakosides A and B. With all the required fragments in hand, we
proceeded to assemble the final targets, plakosides A (1) and B (2), as shown in
Scheme 5. The stereoselective glycosidation of azidosphingosine 13 with galactosyl
Scheme 5. Total Synthesis of Plakosides A (1) and B (2)
a) SnCl2 (3.0equiv.), AgOTf (3.0equiv.), DTBMP (1.2 equiv.), 4-Š MS, CH 2Cl2, 0 ! 258. b) DIBAL
(1.5 equiv.), CH2CH2, À788. c) Prenyl bromide (1.5 equiv.), NaH (1.2 equiv.), DMF, 08. d) Ph3P (2.0equiv.),
H2O (2.0equiv.), benzene, 45 8. e) HOAt (3.1 equiv.), EDC (3.0equiv.), THF, 0 8. f) TBAF (5.0equiv.), THF,
258. h) aq. 1n HCl (cat.), MeOH, 378. Abbreviations: DIBAL ˆ diisobutylaluminium hydride, EDC ˆ 1-[3-
(dimethylamino)propyl]3-ethylcarbodiimide, DTBMP ˆ 2,6-di-(tert-butyl)-4-methylpyridine, HOAt ˆ 1-hy-
droxy-7-azabenzotriazole, TBDMS ˆ (t-Bu)Me2Si, TBDPS ˆ (t-Bu)Ph2Si, TBAF ˆ Bu4NF.

Helvetica Chimica Acta ± Vol. 83 (2000)
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fluoride 11 proceeded in the presence of SnCl2, AgOTf, 2,6-di-(tert-butyl)-4-methyl-
pyridine and 4-Š molecular sieves to afford exclusively the expected b-galactoside 55 in
93% yield [12]. Removal of the pivaloate from 55 with DIBAL furnished hydroxy
compound 56 (98% yield) onto which the prenyl group was installed (NaH,
BrCH2CHˆC(CH3)2) to afford compound 57 (89% yield). Staudinger reduction
[12][24] of the azido group in 57 (Ph3P, H2O, 458) led to amine 58 in 90% yield, which
was then coupled with the acid 12 in the presence of EDC and HOAt to furnish the
desired plakoside A skeleton 59 (85% yield). Finally plakoside A (1) was released from
59 by sequential treatment with TBAF (97% yield of diol 60) and aqueous HCl (96%
yield of 1). Compound 14 was converted to plakoside B (2) via a similar path and in
similar yields (see Scheme 5). Both 1 and 2 exhibited spectroscopic data identical to
those reported for natural plakosides A (1) and B (2) [1].
Synthesis of Plakoside Analogs 3 ± 10. The plakoside analogs 3 ± 5 and 7 ± 9 were
synthesized (Scheme 6) starting from glycosides 56 and 62, respectively, and utilizing
the synthetic technology developed for the construction of the natural plakosides A (1)
and B (2). Thus, O-alkylation of 56 with allyl, geranyl, or benzyl bromide in the
presence of NaH furnished the corresponding ethers (67, 68, and 69, resp.). The N3
groups of these compounds were reduced to afford the expected amines in high overall
yields. Attachments of the a-hydroxy-carboxylic-acid side chain through amide-bond
formation were then followed by the two-step deprotection sequence described above,
affording analogs 3, 4, and 5 in high overall yields (58, 49, and 60% overall yields,
resp.). Analogs 7, 8, and 9 were similarly prepared (69, 57, and 63% overall yields, resp.)
as summarized in Scheme 6.
The syntheses of analogs 6 and 10 followed similar paths as shown in Scheme 7.
Compound 6 was assembled in 58% overall yield from a-hydroxy carboxylic acid
12, 3-O-prenylated azidosphingosine 73, and galactosyl fluoride 74 through glycosida-
tion, azide reduction, amide-bond formation, and sequential removal of protecting
groups. Coupling of 3-O-prenylated galactosyl fluoride 76, a-hydroxy carboxylic acid
12, and azidosphingosine 13 in similar fashion gave compound 10 (60% overall
yield).
Biological Evaluation of Plakosides A (1), B (2), and Analogs 3 ± 10. With the
synthetic plakosides A, B, and their analogs in hand, we proceeded to evaluate their
biological activities in three in vitro assays. We used the mixed-lymphocyte-reaction
(MLR) proliferation assay as an in vitro model for an allogeneic immune response, the
concanavalin A (Con A) response as a model for T cell proliferation in response to
mitogen, and the murine bone marrow cell proliferation assay as a culture system of
primary, non-lymphoid cells. The combination of these assays provided information not
only about the immunosuppressive activity (MLR and Con A response), but also about
the potential cytotoxic and cytostatic effects (bone marrow cell proliferation) of these
compounds. In the MLR assay, spleen cells from CBA and BALB/c mice were used. The
Con A response assay, was performed with Con A-stimulated CBA spleen cells, and the
murine bone marrow cell proliferation assay was performed with bone marrow cells
from CBA mice and conditioned media from the myelomonocytic cell line WEHI-3
and the fibroblast-like cell line L-929 as a source of growth factors. In all assays,
proliferation was measured by [3H]thymidine incorporation. Proliferation of BALB/c
spleen cells alone, of CBA spleen cells without Con A, and of CBA bone marrow cells

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Helvetica Chimica Acta ± Vol. 83 (2000)
Scheme 6. Synthesis of Plakoside Analogs 2 ± 4 and 7 ± 9
a) DIBAL (1.5 equiv.), CH2Cl2, À788. b) Alkyl bromide (1.5 equiv.), NaH (1.2 equiv.), DMF, 08. c) Ph3P
(2.0equiv.), H 2O (2.0equiv.), benzene, 45 8. d) HOAt (3.1 equiv.), EDC (3.0equiv.), THF, 0 8. e) TBAF
(5.0equiv.), THF, 25 8. f) aq. 1n HCl (cat.), MeOH, 378. Abbreviations: DIBAL ˆ diisobutylaluminium hydride,
EDC ˆ 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride, DTBMP ˆ 2,6-di(tert-butyl)-4-meth-
ylpyridine, HOAt ˆ 1-hydroxy-7-azabenzotriazole, TBDMS ˆ (t-Bu)Me2Si, TBDPS ˆ (t-Bu)Ph2Si, TBAF ˆ
Bu4NF
without conditoned media was taken as background (low control) in the MLR, the
Con A response, and the bone marrow proliferation assays, respectively.
[3H]Thymidine uptakes for the high and low controls were measured at
200,000 cpm and 2,200 cpm in the MLR, at 440,000 cpm and 20,000 cpm in the Con A
response, and at 43,000 cpm and 600 cpm in the bone marrow cell proliferation assay,
resulting in signal-to-noise ratios of 90, 22, and 70, respectively. The IC50 values of the
reference compounds cyclosporine A (CsA) [25], a T-cell-selective immunosuppres-
sant, and azathioprine [26], a nucleotide analogue, which interferes with DNA
synthesis and thus generally inhibits cell proliferation, are shown in the Table. CsA
showed a T-cell-selective activity profile; it inhibited the MLR and the Con A response

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Scheme 7. Synthesis of Plakoside Analogs 6 and 10
a) SnCl2 (3.0equiv.), AgOTf (3.0equiv.), DTBMP (1.2 equiv.), 4-Š molecular sieves, CH 2Cl2, 0 ! 258, 6.5 h. b)
Ph3P (2.0equiv.), H 2O (2.0equiv.), benzene, 45 8, 3.5 h. c) HOAt (3.1 equiv.), EDC (3.0equiv.), THF, 0 8, 6 h.
d) aq. 1n HCl (cat.), MeOH, 378, 3 h. e) NaOMe (0.2 equiv.), MeOH, 258, 30min. Abbreviations: EDC ˆ 1-[3-
(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride, DTBMP ˆ 2,6-di-(tert-butyl)-4-methylpyridine,
HOAt ˆ 1-hydroxy-7-azabenzotriazole, TBDMS ˆ (t-Bu)Me2Si, TBDPS ˆ (t-Bu)Ph2Si
with IC50 values of 0.014 and 0.14 mm, respectively, and had no effect on the
proliferation of bone marrow cells (IC50 > 1 mm). In contrast, the anti-proliferative
compound azathioprine was active in all three assays (IC50 values of 0.028 mm for MLR,
0.15 mm for the Con A response, and 0.050 mm for bone marrow cell proliferation).
None of the plakosides showed any selective activity in the MLR and/or the Con A
response (Table). With the exception of compound 3, all plakosides were either
inactive (IC50 > 50 mm) or showed only marginal activity (IC50 of 18 ± 50 mm).
Compound 3 showed an IC50 value of 7.1 mm in the MLR and of 30 mm in the Con A
response. However, bone marrow cell proliferation was inhibited as well with an IC50
value of 3.3 mm.
Plakosides A (1) and B (2) have been suggested in the literature to be
immunosuppressive on activated T cells based on results obtained in a T-cell
proliferation assay where murine lymph node cells were activated with Con A [1]. In

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Table. Inhibitory Effects of Plakosides A (1), B (2), and Their Analogs 3 ± 10 in the MLRa), the Con A
Responseb), and the Bone Marrow Cell c) Proliferation Assays
Compound
IC50 [mm]
MLR
Con A
Response
Bone marrow
cell
proliferation
CsA
Azathioprine
1
2
3
4
5
6
7
0.014
0.028
> 50
x50
7.1
28
> 50
28
> 50
> 50
> 50
> 50
0.14
0.15
> 5050
> 50
303.3
> 5018
> 50
3024
> 5040
> 50
> 5050
> 5029
> 1
0.050
> 50
x50
> 50
8
9
10
a) Equal amounts of spleen cells from CBA and BALB/c mice (1.6 Â 105 from each strain, 3.2 Â 105 in total)
suspended in 200 ml RPMI 1640 medium containing 10% FCS, 100 units/ml penicillin, 100 mg/ml streptomycin,
2 mm l-glutamine, and 50 mm 2-mercaptoethanol (complete RPMI medium) were plated on a 96-well plate. The
b
cultures were incubated for four days at 378 in 5% CO2. ) Spleen cells from CBA mice (2 Â 105 cells per well)
were incubated for two days in complete RPMI medium in the presence of concanavalin A (2 mg/ml). c) Bone
marrow cells (2.5 Â 104 cells per well) prepared from CBA mice were incubated in complete RPMI medium for
four days. Supernatants from the myelomonocytic cell line WEHI-3 and the fibroblast-like cell line L929 were
added as a source of growth factors. In all assays seven 5-fold dilution steps in duplicates per test compound were
added into each well. Proliferation was determined by pulsing the cultures for 5 h with 1 mCi [3H]thymidine. The
concentrations required for 50% inhibition (IC50) were determined by using a four-parameter logistic function.
constrast to our results, both compounds significantly inhibited this assay at all doses
tested (0.01 ± 10 mg/ml) with 50% inhibition at ca. 0 .1mg/ml. However, the dose-
response curves of plakoside A (1) and B (2) were rather flat over a 1000-fold
concentration range and reached a plateau at 60± 70% inhibition. Moreover, a maximal
[3H]-thymidine incorporation of only 575 cpm was observed [1]. Based on our
observations, we consider these compounds to be at best modest immunosuppressive
agents.
Conclusion. ± In conclusion, the total synthesis of b-galactosylceramides plakosides
A (1), B (2) and the synthesis of their analogs 3 ± 10 were accomplished through an
efficient and convergent strategy. These homogenous pure compounds were evaluated
by a MLR, a Con A response, and a murine bone marrow cell proliferation assay, and
found to be only marginally active, except compound 3, which exhibited modest
immunosuppressive properties, but which was also found to be cytotoxic. Nevertheless,
plakosides A (1) and B (2) with the prenyl residue on the carbohydrate moiety may
interfere with some biological process that still remains to be shown.

Helvetica Chimica Acta ± Vol. 83 (2000)
1989
Experimental Part
General. All reactions were carried out under an Ar atmosphere with dry, freshly distilled solvents under
anh. conditions, unless otherwise noted. Anh. solvents were also obtained by passing them through
commercially available alumina columns. Yields refer to the chromatographically and spectroscopically (1H-
and 13C-NMR) homogeneous materials, unless otherwise stated. Reagents were purchased at highest
commercial quality and used without further purification unless otherwise stated. Reactions were monitored
by TLC carried out on 0.25-mm E. Merck silica gel plates (60F-254) with UV light as visualizing agent or p-
anisaldehyde soln. and heat as developing agents. Flash column chromatography (FC) was performed with E.
Merck silica gel (60, particle size 0.040 ± 0.063 mm). M.p.: Thomas Hoover Unimelt cap. melting-point
apparatus; uncorrected. Optical rotations were recorded on a Perkin-Elmer241 polarimeter. IR Spectra were
recorded on a Perkin-Elmer 1600 series FT-IR spectrometer. NMR Spectra: Bruker DRX-600, AMX-500, or
AMX-400 instruments at 295 K, unless otherwise noted, and calibrated using residual undeuterated solvent as
an internal reference. High-resolution mass spectra (HR-MS): VG ZAB-ZSE mass spectrometer under fast-
atom-bombardment (FAB) conditions. Matrix-assisted laser-desorption-ionization (MALDI-FT-MS) MS:
PerSeptive Biosystems VoyagerTM IonSpec mass spectrometer. Electrospray (ESI) MS: API 100 Perkin-Elmer
mass spectrometer. GC/MS: Hewlett Packard 5971A spectrometer.
Phenyl 6-O-[(tert-butyl)diphenylsilyl]-3,4-O-isopropylidene-1-thio-b-d-galactopyranoside (20). To a stirred
soln. of triol 19 (2.72 g, 5.33 mmol) in DMF (15 ml) at 258 was added camphorsulfonic acid (0.12 g, 0.53 mmol).
The mixture was then stirred for 8 h before it was neutralized with Et3N (0.74 ml, 0.53 mmol). The mixture was
concentrated in vacuo. The crude oil was purified by FC (12% AcOEt in hexanes) to afford 20 (82.61 g, 89%).
Colorless oil. Rf 0.44 (silica gel; 30% AcOEt in hexanes). [a]D ˆ ‡9.7 (c ˆ 1.2, CHCl3); Ft-IR (neat): 3402,
2932, 2872, 1429, 1380, 1219, 1081, 1032, 871, 701. 1H-NMR (600 MHz, CDCl3): 7.72 ± 7.70( m, 4 arom. H); 7.58 ±
7.52 (m, 2 arom. H); 7.44 ± 7.35 (m, 6 arom. H); 7.27 ± 7.23 (m, 3 arom. H); 4.45 (d, J ˆ 10.2, HÀC(1)); 4.28
(dd, J ˆ 2.1, 5.4, HÀC(4)); 4.10± 4.08 ( dd, J ˆ 5.5, 6.9, HÀC(3)); 3.99 ± 3.87 (m, HÀC(5), CH2(6)); 3.57 (dt, J ˆ
2.1, 7.9, HÀC(2)); 2.58 (d, J ˆ 2.4, OH); 1.44 (s, Me); 1.33 (s, Me); 1.0 6 (s, t-Bu). 13C-NMR (150MHz, CDCl 3):
135.6; 135.6; 135.6; 135.6; 133.2; 133.2; 132.3; 132.3; 129.7; 129.7; 129.7; 128.9; 128.9; 127.8; 127.7; 127.7; 127.6;
127.6; 110.0; 88.2; 78.9; 76.8; 73.2; 71.5; 62.8; 28.1; 26.7; 26.7; 26.7; 26.3; 19.2. HR-MS (MALDI-FT): 573.2106
‡
‡
([M ‡ Na] , C31H38NaO5SSi ; calc. 573.2101).
Phenyl 6-O-[(tert-butyl)diphenylsilyl]-3,4-O-isopropylidene-1-thio-2-O-(trimethylacetyl)-b-d-galactopyra-
noside (21). To a stirred soln. of 20 (2.00 g, 3.63 mmol) and 4-(dimethylamino)pyridine (22 mg, 0.18 mmol) in
pyridine (20ml) at 0 8 was carefully added PivCl (0.89 ml, 7.26 mmol). The mixture was then refluxed for 2 h
before it was allowed to cool, and then H2O (1 ml) was carefully added. The mixture was diluted with AcOEt
(50ml) and extracted with sat. aq. CuSO 4 soln. (25 ml), H2O (25 ml), sat. NaHCO3 (3 Â 15 ml) and brine
(25 ml). The org. layer was dried (MgSO4) and concentrated in vacuo. The crude syrup was purified by FC (20%
AcOEt in hexanes) to afford 21 (2.29 g, 99%). White foam. Rf 0.79 (silica gel; 30% AcOEt in hexanes). [a]D
ˆ
À0.9 (c ˆ 2.9, CHCl3). FT-IR (neat): 3422, 2964, 1730, 1479, 1283, 1150, 1109, 1050, 702, 503. 1H-NMR
(600 MHz, CDCl3): 7.70± 7.69 ( m, 4 arom. H); 7.48 ± 7.46 (m, 2 arom. H); 7.43 ± 7.33 (m, 6 arom. H); 7.23 ± 7.21
(m, 3 arom. H); 5.03 (dd, J ˆ 7.1, 10.2, HÀC(2)); 4.62 (d, J ˆ 10.3, HÀC(1)); 4.27 (dd, J ˆ 1.9, 5.3, HÀC(4));
4.16 (d, J ˆ 5.5, 6.8, HÀC(3)); 4.00 ± 3.89 (m, HÀC(5), CH2(6)); 1.50( s, Me); 1.32 (s, Me); 1.26 (s, t-Bu); 1.06
(s, t-Bu). 13C-NMR (150MHz, CDCl 3): 176.8; 135.6; 135.6; 135.6; 135.6; 134.1; 133.2; 133.2; 131.6; 131.6; 129.7;
129.7; 128.9; 128.9; 127.7; 127.7; 127.6; 127.6; 127.5; 110.0; 86.5, 77.2; 76.9; 73.4; 70.9; 63.0; 38.7; 27.7; 27.1;
‡
‡
27.1; 27.1; 26.7; 26.7; 26.7; 26.4; 19.2. HR-MS (MALDI-FT): 657.2684 ([M ‡ Na] , C36H46NaO6SSi ; calc.
657.2677).
6-O-[(tert-Butyl)diphenylsilyl]-3,4-O-isopropylidene-2-O-(trimethylacetyl)-a-d-galactopyranosyl Fluoride
(11a) and 6-O-[(tert-Butyl)diphenylsilyl]-3,4-O-isopropylidene-2-O-(trimethylacetyl)-b-d-galactopyranosyl
Fluoride (11b). To a stirred soln. of 21 (0.98 g, 1.54 mmol) in CH2Cl2 (3 ml) at 08 was added diethylaminosulfur
trifluoride (0.76 ml, 5.76 mmol), followed by dropwise addition of dimethyl(methylthio)sulfonium triflate
(0.59 g, 2.31 mmol) in CH2Cl2 (2 ml) via syringe. The mixture was stirred at 08 for 1 h before it was slowly
warmed up to 258 over a period of 3 h. The mixture was quenched with cold sat. aq. NaHCO3 soln. (5 ml) and
was diluted with AcOEt (30ml). The layers were separated, and the org. layer was washed with sat. aq.
NaHCO3 soln. (15 ml), H2O (15 ml), and brine (15 ml). The org. layer was dried (MgSO4) and concentrated in
vacuo. The crude oil was purified by FC (6% AcOEt in hexanes) to afford the b-anomer 11b (765 mg, 91%) and
the a-anomer 11a (34 mg, 3%) as faintly yellow oils.
Data of the b-Anomer (11b): Rf 0.53 (silica gel; 17% AcOEt in hexanes). [a]D ˆ ‡16.4 (c ˆ 0.5, CHCl3).
FT-IR (neat): 2935, 1740, 1475, 1389, 1218, 1107, 802, 702, 503. 1H-NMR (500 MHz, CDCl3): 7.72 ± 7.65

1990
Helvetica Chimica Acta ± Vol. 83 (2000)
(m, 4 arom. H); 7.48 ± 7.36 (m, 6 arom. H); 5.34 (dd, J ˆ 4.7, 55.3, HÀC(1)); 5.03 (m, HÀC(2)); 4.50( d, J ˆ 6.8,
HÀC(4)); 4.23 (dd, J ˆ 4.5, 6.7, HÀC(3)); 4.05 ± 3.99 (m, HÀC(5), HÀC(6a)); 3.96 ± 3.91 (m, HÀC(6b)); 1.53
(s, Me); 1.36 (s, Me); 1.23 (s, t-Bu); 1.07 (s, t-Bu). 13C-NMR (150MHz, CDCl 3): 176.7; 135.6; 135.6; 135.5;
135.5; 133.2; 133.1; 129.8; 129.7; 127.9; 127.7; 127.7; 127.6; 127.6; 110.4; 105.4 (d, J(C,F) ˆ 867.6, C(1)); 73.4
(d, J(C,F) ˆ 14.5, C(F)); 71.9 (C(3)); 71.3 (C(4)); 69.6 (d, J(C,F) ˆ 110.5, C(2)); 62.6 (C(6)); 38.8; 27.0; 27.0;
‡
‡
27.0; 26.7; 26.7; 26.7; 26.2; 19.2. HR-MS (MALDI-FT): 567.2548 [ M ‡ Na] (C30H41FNaO6Si ; calc. 567.2554).
Data of a-Anomer (11a): Rf 0.61 (silica gel; 17% AcOEt in hexanes). [a]D ˆ ‡40.3 (c ˆ 1.5, CHCl3). FT-IR
(neat): 2935, 1737, 1476, 1380, 1220, 1070, 920, 820, 703, 505. 1H-NMR (500 MHz, CDCl3): 7.72 ± 7.67
(m, 4 arom. H), 7.47 ± 7.33 (m, 6 arom. H); 5.60( dd, J ˆ 2.9, 54.1, HÀC(1)); 4.96 (ddd , J ˆ 3.0, 7.0, 22.7,
HÀC(2)); 4.50± 4.38 ( m, HÀC(3), HÀC(4)); 4.33 (m, HÀC(5)); 4.01 ± 3.88 (m, CH2(6)); 1.49 (s, Me); 1.36
(s, Me); 1.24 (s, t-Bu); 1.05 (s, t-Bu). 13C-NMR (150MHz, CDCl 3): 177.7; 135.6; 135.6; 135.5; 135.5; 133.2; 133.2;
129.7; 129.7; 127.7; 127.7; 127.6; 127.6; 109.9; 104.3 (d, J(C,F) ˆ 900.0, C(1)); 72.7 (C(3)); 70.2 (C(4)); 70.2
(d, J(C,F) ˆ 100.0, C(2)); 70.1 (d, J(C,F) ˆ 25.0, C(5)); 62.3 (C(6)); 38.8; 27.6; 27.0; 27.0; 27.0; 26.7; 26.7; 26.7;
‡
‡
26.1; 19.2. HR-MS (MALDI-FT): 567.2570[ M ‡ Na] (C30H41FNaO6Si ; calc. 567.2554).
(2Z)-Tridec-2-en-1-ol (23). A mixture of tridec-2-yn-1-ol (22) (10.3 g, 51.75 mmol) and 5% Pd on BaSO4
(0.71 g) in pyridine (200 ml) was stirred at 258 under 1 atm H2 for 10h. The catalyst was removed through a pad
of Celite and rinsed with AcOEt (100 ml). The filtrate was concentrated in vacuo at 508. The residue was taken
up in AcOEt (400 ml) and extracted with sat. aq. CuSO4 soln. (100 ml), H2O (2 Â 100 ml), and brine (100 ml).
The org. layer was dried (MgSO4) and concentrated in vacuo to give the crude product as a faintly yellow liquid.
The crude product was then purified by FC (silica gel; 10% AcOEt in hexanes) to afford 23 (9.99 g, 96%). Clear
liquid. Rf 0.44 (silica gel; 25% AcOEt in hexanes). FT-IR (neat): 3331, 3015, 2922, 2853, 1464, 1378, 1016, 721.
1H-NMR (500 MHz, CDCl3): 5.63 ± 5.50( m, 2 H); 4.17 (t, J ˆ 4.4, 2 H); 2.05 (q, J ˆ 5.8, 2 H); 1.34 ± 1.24
(m, 13 H); 0.86 (t, J ˆ 6.8, 3 H). 13C-NMR (125 MHz, CDCl3): 134.2; 129.1; 59.5; 32.8; 30.5 (3 C); 30.3; 30.2;
‡
‡
30.1; 28.3; 23.5; 15.0. GS/MS: 198 M (C13H26O ; calc. 198).
[(1R,2S)-2-Decylcyclopropyl]methanol (25). To a mixture of dioxaborolane 24 (18.77 g, 62.92 mmol), 23
(10.40 g, 52.44 mmol), and activated 4-Š molecular sieves (2.00 g) in CH2Cl2 at À158 was dropwise added a
freshly prepared soln. of Zn(CH2I)2 ´ DME complex via cannula kept at À158 over a period of 1 h at a rate to
keep the internal temp. below À108. The mixture was stirred at À108 for 2 h and then allowed to warm to 258
slowly over a period of 4 h. A sat. aq. NH4Cl soln. (100 ml) was added to the mixture, and the layers were
separated. The aq. layer was further extracted with Et2O (3 Â 250ml). The combined org. layers were stirred
vigorously with 5n aq. KOH soln. (300 ml) at 258 for 12 h. The biphasic mixture was separated, and the org.
layer was successively extracted with 1n aq. HCl soln. (2 Â 100 ml), sat. aq. NaHCO3 soln. (2 Â 100 ml), H2O
(100 ml), brine (100 ml), dried (MgSO4), and concentrated in vacuo. The oily residue was purified by FC (silica
gel; 15% AcOEt in hexanes) to afford 24 (10.67 g, 96%). Clear liquid. Rf 0.43 (silica gel; 25% AcOEt in
hexanes). [a]D ˆ ‡19.7 (c ˆ 5.7, CHCl3); FT-IR (neat): 3346, 3063, 2993, 2934, 2854, 1462, 1380, 1028, 721.
1H-NMR (500 MHz, CDCl3): 3.65 ± 3.52 (m, 2 H); 1.45 ± 1.33 (m, 3 H); 1.32 ± 1.16 (m, 16 H); 1.11 ± 1.03
(m, 1 H); 0.85 (t, J ˆ 6.5, 3 H); 0.85 ± 0.81 (m, 1 H); 0.69 ± 0.65 (m, 1 H); À0.07 (m, 1 H). 13C-NMR
(125 MHz, CDCl3): 63.3; 31.9; 30.2; 29.6 (3 C); 29.5; 29.3; 28.5; 22.7; 18.1; 16.1; 14.1; 9.4. HR-MS (FAB):
‡
‡
235.2041 ([M ‡ Na] , C14H28NaO ; calc. 235.2038).
10-[(1S,2R)-2-(Iodomethyl)cyclopropyl]decane (26). To a soln. of 25 (17.01 g, 80.10 mmol), imidazole
(7.47 g, 109.73 mmol), and Ph3P (27.31 g, 104.12 mmol) in a mixture of MeCN/E2O (270ml, 3 :5 ( v :v)) at 08 was
added I2 (30.49 g, 120.12 mmol) in five portions over 30 min under Ar in the dark. The resulting yellow mixture
was stirred at 08 for 30min before it was diluted with Et 2O (300 ml) and washed successively with sat. aq.
Na2S2O3 soln. (2 Â 125 ml), aq. CuSO4 soln. (2 Â 100 ml), H2O (100 ml), and brine (100 ml). The org. layer was
dried (MgSO4) and concentrated in vacuo in the dark. The crude residue was purified by FC in the dark (silica
gel; 6% Et2O in hexanes) to afford 26 (24.79 g, 96%). Clear liquid. Rf 0.88 (silica gel; 9% Et2O in hexanes).
1
[a]D ˆ ‡0.2 (c ˆ 4.6, CHCl3). FT-IR (neat): 2923, 2852, 1461, 1377, 1170, 1024, 721, 600. H-NMR (500 MHz,
CDCl3): 3.29 (dd, J ˆ 8.0, 14.0, 1 H); 3.18 (dd, J ˆ 8.0, 14.0, 1 H); 1.55 ± 1.48 (m, 1 H); 1.42 ± 1.33 (m, 3 H); 1.32 ±
1.19 (m, 13 H); 1.17 ± 1.09 (m, 1 H); 1.07 ± 0.99 (m, 1 H); 0.85 (t, J ˆ 6.5, 3 H); 0.85 ± 0.81 (m, 1 H); 0.69 ± 0.65
(m, 1 H); À0.07 (m, 1 H). 13C-NMR (125 MHz, CDCl3): 31.9; 30.1; 29.7 (3 C); 29.5; 29.3; 27.5; 22.7; 21.8; 20.4;
‡
‡
16.1; 14.1; 9.7. HR-MS (MALDI-FT): 195.2114 ([M À I] , C14H27 ; calc. 195.2113).
10-{(1S,2R)-2-[8-(Tetrahydro-2H-pyran-2-yl)-octyl]cyclopropyl}decane (28). To a soln. of 26 (9.53 g,
29.55 mmol) in THF (75 ml) at 08 in the dark was added via cannula the Grignard reagent 27, prepared from
THPOCH2(CH2)5CH2Br (13.18 g, 44.33 mmol) and Mg (1.33 g, 54.67 mmol) in THF (100 ml). The mixture was
stirred at 08 for 5 min before addition of a soln. of Li2CuCl4, prepared from LiCl (7.5 mg, 0.18 mmol) and anh.
CuCl2 (11.9 mg, 0.09 mmol) in dry THF (1 ml). The resulting mixture was stirred at 08 for additional 30min

Helvetica Chimica Acta ± Vol. 83 (2000)
1991
before quenching with H2O (2 ml). The mixture was diluted with Et2O (400 ml), and extracted successively with
1n aq. HCl soln. (125 ml), H2O (100 ml), and brine (100 ml). The org. layer was dried (MgSO4) and
concentrated in vacuo. The crude residue was then purified by FC (silica gel; 100% hexanes) to afford 28
(10.13 g, 87%). Clear liquid. Rf 0.21 (silica gel; 100% hexanes). [a]D ˆ ‡0.3 (c ˆ 1.1, CHCl3); FT-IR (neat):
2925, 2854, 1460, 1124, 1073, 1034. 1H-NMR (600 MHz, CDCl3): 4.55 (t, J ˆ 3.1, 1 H); 3.87 ± 3.83 (m, 1 H); 3.73 ±
3.69 (m, 1 H); 3.49 ± 3.46 (m, 1 H); 3.37 ± 3.34 (m, 1 H); 1.83 ± 1.78 (m, 1 H); 1.72 ± 1.68 (m, 1 H); 1.60± 1.45
(m, 6 H); 1.40± 1.15 ( m, 28 H); 1.15 ± 1.09 (m, 2 H); 0.86 (t, J ˆ 7.0, 3 H); 0.65 ± 0.60 (m, 2 H); 0.58 ± 0.52
(m, 1 H); À0.34 (m, 1 H). 13C-NMR (150MHz, CDCl 3): 98.8; 67.7; 62.3; 31.9; 30.8; 30.2; 30.2; 29.8; 29.7; 29.7;
29.7; 29.7; 29.7; 29.6; 29.6; 29.5; 29.4; 28.7; 28.7; 26.2; 25.5; 22.7; 19.7; 15.8; 14.1; 10.9. LR-MS (ESI): 417 ([M ‡
‡
‡
Na] , C26H50NaO2 ; calc. 417).
8-[(1R,2S)-2-Decylcyclopropyl]octan-1-ol (29). To a soln. of 18 (7.60g, 19.26 mmol) in MeOH (300ml)
was added pyridinium toluene-4-sulfonate (0.97 g, 3.85 mmol). The mixture was then heated at 558 for 5 h
before it was cooled and concentrated in vacuo. The residue was then taken up in Et2O (250ml), and washed
with sat. aq. NaHCO3 soln. (100 ml), and brine (100 ml). The org. layer dried (MgSO4) and concentrated in
vacuo. The crude product was purified by FC (silica gel; 10% AcOEt in hexanes) to afford 29 (5.86 g, 98%).
White, waxy solid. Rf 0.39 (silica gel; 10% AcOEt in hexanes). M.p. 59 ± 608 (Et2O). [a]D ˆ ‡0.3 (c ˆ 0.9,
CHCl3). FT-IR (CHCl3): 3333, 2924, 2853, 1698, 1651, 1558, 1458, 1422, 1052, 751. 1H-NMR (600 MHz, CDCl3):
3.62 (t, J ˆ 6.6, 2 H); 1.58 ± 1.52 (m, 2 H); 1.42 ± 1.18 (m, 29 H); 1.17 ± 1.14 (m, 2 H); 0.86 (t, J ˆ 7.0, 3 H); 0.65 ±
0.60 (m, 2 H); 0.58 ± 0.52 (m, 1 H); À0.38 (m, 1 H). 13C-NMR (150MHz, CDCl 3): 63.1; 32.8; 31.9; 30.2; 30.2;
‡
29.7 (5 C); 29.6; 29.4; 29.4; 28.7; 28.7; 25.7; 22.7; 15.8; 15.7; 14.1; 10.9. HR-MS (FAB): 311.3310 ([M ‡ H] ,
‡
C21H42O ; calc. 311.3314).
8-[(1R,2S)-2-Decylcyclopropyl]octanal (30). To a soln. of oxalyl chloride (1.87 ml, 21.01 mmol) in CH2Cl2
(75 ml) at À788 was dropwise added a soln. of DMSO (1.99 ml, 28.01 mmol) in CH2Cl2 (15 ml). The mixture was
stirred at À788 for 30min before the dropwise addition of 29 (4.35 g, 14.01 mmol) in CH2Cl2 (20ml) via
cannula. The mixture was stirred further at À788 for 30min and then Et 3N (9.76 ml, 70.05 mmol) was dropwise
added. The mixture was stirred for 30min at À788 before it was allowed to warm to 258 over a period of 30min.
The mixture was diluted with Et2O (150ml) and washed with sat. aq. NH 4Cl soln. (2 Â 75 ml), H2O (75 ml), and
brine (75 ml). The org. layer was dried (MgSO4) and concentrated in vacuo. The crude residue was purified by
FC (silica gel; 5% Et2O in hexanes) to afford 30 (4.18 g, 96%). Clear liquid. Rf 0.36 (silica gel; 10% Et2O in
hexanes). [a]D ˆ ‡0.4 (c ˆ 1.3, CHCl3). FT-IR (neat): 30.58, 2922, 2853, 2711, 1729, 1465, 1388, 1020, 722.
1H-NMR (500 MHz, CDCl3): 9.73 (t, J ˆ 2.0, 1 H); 3.39 (dt, J ˆ 5.0, 10.0, 2 H); 1.64 ± 1.55 (m, 2 H); 1.42 ± 1.15
(m, 26 H); 1.17 ± 1.07 (m, 2 H); 0.84 (t, J ˆ 7.5, 3 H); 0.65 ± 0.58 (m, 2 H); 0.55 ± 0.52 (m, 1 H); À0.37 (m, 1 H).
13C-NMR (125 MHz, CDCl3): 202.8; 43.9; 31.9; 30.2; 30.1; 29.7 (4 C); 29.4; 29.4; 29.3; 29.1; 28.7; 28.6; 22.7; 22.1;
‡
‡
15.7; 15.7; 14.1; 10.9. HR-MS (FAB): 331.2975 ([M ‡ Na] , C21H40NaO ; calc. 331.2977).
Ethyl (E)-10-[(1R,2S)-2-Decylcyclopropyl]dec-2-enoate (31). To a soln. of triethyl phosphonoacetate
(1.76 ml, 7.05 mmol) in THF (10 ml) at 08 was added NaH (60% in mineral oil; 0.28 g, 7.05 mmol). The resulting
mixture was stirred for 15 min at 08 before the dropwise addition of 30 (1.45 g, 4.69 mmol) in THF (15 ml) via
syringe. The mixture was stirred further for 25 min at 08 before it was quenched with sat. aq. NH4Cl soln. (3 ml).
The mixture was diluted with Et2O (150ml) and washed with sat. aq. NH 4Cl soln. (75 ml), H2O (75 ml), and
brine (75 ml). The org. layer was dried (MgSO4) and concentrated in vacuo. The crude residue was then purified
by FC (silica gel; 5% Et2O in hexanes) to afford the desired (E)-ester 31 (1.66 g, 94%) and a trace of the less
polar undesired (Z)-ester (0.08 g, 4%) as clear oils. 31: Rf 0.36 (silica gel; 10% Et2O in hexanes). [a]D ˆ À0.1
(c ˆ 1.5, CHCl3). FT-IR (neat): 2924, 2855, 1723, 1654, 1459, 1368, 1307, 1265, 1180, 1045, 980, 720 cmÀ1
;
1H-NMR (600 MHz, CDCl3): 6.97 ± 6.93 (m, 1 H); 5.80± 5.78 ( m, 1 H); 4.17 (q, J ˆ 7.1, 10.0, 2 H); 2.19 ± 2.15
(m, 2 H); 1.50± 1.39 ( m, 2 H); 1.39 ± 1.15 (m, 29 H); 1.17 ± 1.07 (m, 2 H); 0.86 (t, J ˆ 7.0, 3 H); 0.65 ± 0.58
(m, 2 H); 0.55 ± 0.52 (m, 1 H); À0.35 (m, 1 H). 13C-NMR (150MHz, CDCl 3): 166.8; 149.5; 121.2; 60.1; 32.2;
31.9; 30.2; 30.2; 29.7 (4 C); 29.5; 29.4; 29.4; 29.2; 28.7; 28.7; 28.0; 22.7; 15.8; 15.7; 14.3; 14.1; 10.9. HR-MS (FAB):
‡
‡
379.3568 ([M ‡ H] , C25H46O2 ; calc. 379.3576).
Ethyl (2S,3R)-10-[(1R,2S)-2-Decylcyclopropyl]-2,3-dihydroxydecanoate (32). To a mixture of tBuOH
(30ml) and H 2O (30ml) at 25 8 were added K2Os2(OH)4 (4.4 mg), (DHQD)2-PHAL (47 mg), K3Fe(CN)6
(5.96 g), K2CO3 (2.50g), and MeSO 2NH2 (0.58 g, 6.08 mmol). The resulting mixture was stirred to produce a
biphasic mixture before cooling to 08 and subsequent addition of 31 (2.30g, 6.08 mmol). The mixture was then
stirred at 08 for 8 h. Na2SO3 (9.00 g) was added to the mixture at 08 before it was allowed to warm to 258 and was
stirred for additional 40min. The mixture was diluted with AcOEt (150ml), and the aq. layer was further
extracted with AcOEt (2 Â 75 ml). The combined org. layers were extracted with 2n aq. KOH soln. (75 ml),
H2O (75 ml), and brine (75 ml), and dried (MgSO4) and concentrated in vacuo to give the crude product, which

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Helvetica Chimica Acta ± Vol. 83 (2000)
was purified by FC (silica gel; 20% AcOEt in hexanes) to afford 32 (2.31 g, 92%). Waxy white solid. Rf 0.29
(silica gel; 20% AcOEt in hexanes). M.p. 58 ± 618 (AcOEt). [a]D ˆ ‡7.2 (c ˆ 1.0, CHCl3). FT-IR (CHCl3 soln.):
3357, 2916, 2849, 1717, 1465, 1383, 1291, 1130, 1036, 602. 1H-NMR (500 MHz, CDCl3): 4.28 (q, J ˆ 7.0, 2 H); 4.07
(br. s, 1 H); 3.88 (t, J ˆ 2.2,1 H); 3.02 (br. s, OH); 1.83 (br. s, OH); 1.63 ± 1.55 (m, 2 H); 1.50± 1.41 ( m, 1 H);
1.41 ± 1.15 (m, 30H); 1.15 ± 1.07 ( m, 2 H); 0.87 (t, J ˆ 7.0, 3 H); 0.65 ± 0.58 (m, 2 H); 0.55 ± 0.52 (m, 1 H); À0.34
(m, 1 H). 13C-NMR (125 MHz, CDCl3): 164.2; 72.9; 72.5; 62.1; 33.9; 31.9; 30.2; 30.2; 29.7 (3 C); 29.6; 29.6; 29.6;
‡
‡
29.5; 29.4; 28.7; 28.7; 25.7; 22.7; 15.7; 15.7; 14.2; 14.1; 10.9. HR-MS (FAB): 435.3456 ([M ‡ H] ; C25H48O4 ; calc.
435.3450).
Ethyl (2S,3R)-10-[(1R,2S)-2-Decylcyclopropyl]-3-hydroxy-2-[(4-nitrophenylsulfonyl)oxy]decanoate (33).
To a soln. of 32 (1.32 g, 3.20mmol) in pyridine (30ml) at 0 8 was added 4-nitrobenzenesulfonyl chloride (0.79 g,
3.20mmol) in one portion. The resulting mixture was stirred at 0 8 for 7.5 h before it was quenched with icy cold
H2O (2 ml). The mixture was diluted with cold Et2O (200 ml) and extracted with cold sat. aq. CuSO4 soln.
(50ml), cold H 2O (2 Â 100 ml), and cold brine (100 ml). The org. layer was dried (MgSO4) and concentrated in
vacuo below 108. The crude residue was then purified by FC (silica gel; 12% chilled AcOEt in hexanes) to afford
33 (1.59 g, 90%) as a clear oil, which solidified to a white solid upon standing. Rf 0.30 (silica gel; 20% AcOEt in
hexanes). [a]D ˆ ‡1.0( c ˆ 2.7, CHCl3). FT-IR (neat): 3532, 2924, 2853, 1759, 1537, 1465, 1372, 1350, 1313, 1188,
1
1095, 1024, 855, 740. H-NMR (500 MHz, CDCl3): 8.38 (dd, J ˆ 2.0, 7.0, 2 H); 8.16 (dd, J ˆ 2.0, 7.0, 2 H); 4.97
(d, J ˆ 3.0, 1 H); 4.15 (q, J ˆ 7.0, 2 H); 4.10 ± 4.07 (m, 1 H); 1.76 (d, J ˆ 9.0, 1 H); 1.60 ± 1.40 (m, 3 H); 1.41 ± 1.15
(m, 31 H); 1.15 ± 1.07 (m, 1 H); 0.86 (t, J ˆ 7.0, 3 H); 0.65 ± 0.58 (m, 2 H); 0.55 ± 0.52 (m, 1 H); À0.35 (m, 1 H).
13C-NMR (125 MHz, CDCl3): 166.8; 150.7; 141.9; 129.5; 129.5; 124.2; 124.2; 80.9; 71.7; 62.4; 33.1; 31.9; 30.2; 30.1;
29.7 (3 C); 29.5; 29.5; 29.3; 29.3; 28.7; 28.6; 25.3; 22.7; 15.7; 15.7; 14.1; 14.1; 14.0; 10.9. HR-MS (FAB): 620.3216
‡
‡
([M ‡ Na] , C31H51O8NNaS ; calc. 620.3233).
Ethyl (2R,3R)-2-Azido-10-[(1R,2S)-2-decylcyclopropyl]-3-hydroxydecanoate (34).
A mixture of 33
(0.50 g, 0.91 mmol) and NaN3 (0.37 g, 5.61 mmol) in DMF (5 ml) was stirred at 258 for 36 h. The mixture was
diluted with Et2O (25 ml) and washed with H2O (2 Â 10ml) and brine (100ml). The org. layer was dried
(MgSO4) and concentrated in vacuo. The crude residue was then purified by FC (silica gel; 20% Et2O in
hexanes) to afford 34 (0.37 g, 94%). Clear oil. Rf 0.80 (silica gel; 20% AcOEt in hexanes). [a]D ˆ ‡3.7 (c ˆ 1.6,
CHCl3). FT-IR (neat): 3422, 2924, 2853, 2109, 1736, 1465, 1384, 1255, 1190, 1022, 855. 1H-NMR (400 MHz,
CDCl3): 4.28 (dq, J ˆ 0.8, 7.0, 2 H); 3.94 ± 3.88 (m, 2 H); 2.23 (d, J ˆ 6.2, 1 H); 1.60± 1.40 ( m, 3 H); 1.41 ± 1.15
(m, 30H); 1.15 ± 1.07 ( m, 2 H); 0.85 (t, J ˆ 6.7, 3 H); 0.65 ± 0.58 (m, 2 H); 0.55 ± 0.52 (m, 1 H); À0.35 (m, 1 H).
13C-NMR (100 MHz, CDCl3): 169.0; 71.9; 66.2; 62.1; 33.1; 31.9; 30.2; 30.2; 29.7 (3 C); 29.5; 29.5; 29.4; 29.4; 28.7;
‡
‡
28.6; 25.4; 22.7; 15.7; 15.7; 14.2; 14.1; 14.0; 10.9. HR-MS (FAB): 460.3507 ([M ‡ Na] , C25H47N3NaO3 ; calc.
460.3515).
Ethyl (2R,3R)-2-Azido-3-[(tert-butyl)dimethylsilyloxy]-10-[(1R,2S)-2-decylcyclopropyl]decanoate (35).
To a stirred soln. of 34 (0.79 g, 1.81 mmol) and 2,6-lutidine (0.53 ml, 4.51 mmol) in CH2Cl2 (8 ml) at À788 was
added dropwise TBDMSOTf (0.44 ml, 1.90 mmol) via syringe. The mixture was allowed to warm to 258 and was
stirred further for 30min before it was diluted with Et 2O (25 ml) and extracted successively with sat. aq. CuSO4
soln. (5 ml), H2O (10ml), and brine (5 ml). The org. layer was dried (MgSO 4) and concentrated in vacuo to
afford 35 (1.00 g, 100%). Faintly yellow oil. Rf 0.72 (silica gel; 10% AcOEt in hexanes). [a]D ˆ À8.01 (c ˆ 2.8,
CHCl3). FT-IR (neat): 2926, 2855, 2108, 1748, 1464, 1373, 1256, 1187, 1113, 1027, 837, 777. 1H-NMR (600 MHz,
CDCl3): 4.22 (dq, J ˆ 0.8, 7.1, 2 H); 4.09 ± 4.06 (m, 1 H); 3.95 (d, J ˆ 5.0, 1 H); 1.64 ± 1.59 (m, 1 H); 1.50± 1.40
(m, 1 H); 1.39 ± 1.15 (m, 33 H); 1.15 ± 1.07 (m, 2 H); 0.89 ± 0.84 (m, 12 H); 0.65 ± 0.58 (m, 2 H); 0.55 ± 0.52
(m, 1 H); 0 .0 8 s(, 5 H); À0.35 (m, 1 H). 13C-NMR (150MHz, CDCl 3): 168.6; 73.3; 66.4; 61.7; 33.2; 32.0; 30.3;
30.2; 29.7 (3 C); 29.6; 29.5; 29.5; 29.4; 28.7; 28.6; 25.7; 25.7; 25.7; 24.7; 22.7; 18.0; 15.7; 15.7; 14.2; 14.1; 14.1; 10.9;
‡
‡
À4.5, À4.7. HR-MS (MALDI-FT): 574.4389 ([M ‡ Na] , C31H63N3NaO3Si ; calc. 574.4380).
(2S,3R)-1-Azido-3-[(tert-butyl)dimethylsilyloxy]-10-[(1R,2S)-2-decylcyclopropyl]decan-1-ol (13). To
a
stirred soln. of 35 (0.28 g, 0.50 mmol) in THF (8 ml) at 08 was added dropwise a soln. of LiBH4 (2.0m in
THF, 1 ml, 2.00 mmol). The mixture was stirred at 08 for 1.5 h before it was allowed to warm to 258 over a period
of 2 h. The mixture was quenched carefully with MeOH (1 ml), diluted with AcOEt (10ml), and was washed
successively with H2O (5 ml) and brine (5 ml). The org. layer was dried (MgSO4) and concentrated in vacuo.
The crude residue was then purified by FC (silica gel; 17% AcOEt in hexanes) to afford 13 (0.25 g, 95%).
Faintly yellow liquid. Rf 0.38 (silica gel; 10% AcOEt in hexanes). [a]D ˆ À2.9 (c ˆ 2.0, CHCl3). FT-IR (neat):
3372, 2926, 2855, 2101, 1464, 1368, 1256, 1080, 1042, 837, 776. 1H-NMR (500 MHz, CDCl3): 3.82 ± 3.70( m, 2 H);
3.50± 3.45 ( m, 1 H); 2.20± 2.15 ( m, 1 H); 1.64 ± 1.56 (m, 1 H); 1.50± 1.40( m, 1 H); 1.39 ± 1.15 (m, 29 H); 1.15 ±
1.07 (m, 2 H); 0.89 ± 0.84 (m, 12 H); 0.65 ± 0.58 (m, 2 H); 0.55 ± 0.52 (m, 1 H); 0.10 (s, 3 H); 0 .0 7s(, 3 H); À0.35
(m, 1 H). 13C-NMR (125 MHz, CDCl3): 73.4; 66.5; 62.2; 33.9; 31.9; 30.2; 30.1; 29.7 (3 C); 29.5; 29.5; 29.4; 28.7;

Helvetica Chimica Acta ± Vol. 83 (2000)
1993
28.7; 25.8; 25.8; 25.8; 24.8; 22.8; 24.9; 22.7; 18.0; 15.7; 15.7; 14.1; 10.9; À4.5; À4.6. HR-MS (FAB): 642.3418
‡
‡
([M ‡ Cs] , C29H59CsN3O2Si ; calc. 642.3431).
9-[(1R,2S)-2-Decylcyclopropyl]-1-[(tetrahydo-2H-pyran-2-yl)oxy]non-4-yne (37). To a soln. of 26 (8.68 g,
26.92 mmol) in THF (75 ml) at 08 in the dark was added via cannula the Grignard reagent 36, prepared from
THPOCH2(CH2)2CꢀC(CH2)2CH2Br (11.67 g, 40.38 mmol) and Mg (1.21 g, 49.80 mmol) in THF (100 ml). The
mixture was stirred at 08 for 5 min before the addition of a soln. of Li2CuCl4, prepared from LiCl (6.8 mg,
0.16 mmol) and anh. CuCl2 (11 mg, 0.08 mmol) in dry THF (1 ml). The resulting mixture was stirred at 08 for
additional 30min before quenching with H 2O (2 ml). The mixture was diluted with Et2O (400 ml) and extracted
successively with 1n aq. HCl soln. (125 ml), H2O (100 ml), and brine (100 ml). The org. layer was dried
(MgSO4) and concentrated in vacuo. The crude residue was then purified by FC (silica gel; 100% hexanes) to
afford 37 (9.16 g, 84%). Clear oil. Rf 0.51 (silica gel; 10% Et2O in hexanes). [a]D ˆ ‡0.2 (c ˆ 1.5, CHCl3). FT-IR
(neat): 2926, 2854, 1460, 1121, 1066, 1034, 991. 1H-NMR (600 MHz, CDCl3): 4.58 (t, J ˆ 4.0, 1 H); 3.85 ± 3.78
(m, 2 H); 3.49 ± 3.42 (m, 2 H); 2.25 ± 2.23 (m, 2 H); 2.13 ± 2.11 (m, 2 H); 1.83 ± 1.65 (m, 4 H); 1.59 ± 1.54
(m, 2 H); 1.54 ± 1.42 (m, 6 H); 1.40± 1.20 ( m, 18 H); 1.15 ± 1.11 (m, 2 H); 0.86 (t, J ˆ 6.5, 3 H); 0.63 (m, 2 H);
0.55 (m, 1 H); À0.28 ± À 0.34 (m, 1 H). 13C-NMR (150MHz, CDCl 3): 98.8; 80.58; 79.4; 66.1; 62.1; 31.9; 30.7;
30.2; 29.7; 29.7; 29.7; 29.7; 29.4; 29.4; 29.3; 29.1; 28.7; 28.2; 25.5; 22.7; 19.5; 18.8; 15.8; 15.6; 15.6; 14.1; 10.9. HR-
‡
‡
MS (MALDI-FT): 427.3546 ([M ‡ Na] , C27H48NaO2 ; calc. 427.3552).
9-[(1R,2S)-2-Decylcyclopropyl]dec-4-yn-1-ol (38). To a soln. of 37 (9.08 g, 22.45 mmol) in MeOH
(300 ml) was added pyridium toluene-4-sulfonate (1.13 g, 4.49 mmol). The mixture was heated at 558 for 5 h
before it was cooled and concentrated in vacuo. The residue was then taken up in Et2O (250ml) and washed
with sat. aq. NaHCO3 soln. (100 ml) and brine (100 ml). The org. layer was dried (MgSO4) and concentrated in
vacuo. The residue was then purified by FC (silica gel; 5% AcOEt in hexanes) to afford 38 (7.20 g, 100%). Clear
oil. Rf 0.55 (silica gel; 12% AcOEt in hexanes). [a]D ˆ ‡0.5 (c ˆ 2.5, CHCl3). FT-IR (neat): 3332, 2925, 2854,
1
1460, 1331, 1058, 930, 721. H-NMR (600 MHz, CDCl3): 3.74 (q, J ˆ 4.8, 2 H); 2.28 ± 2.25 (m, 2 H); 2.14 ± 2.12
(m, 2 H); 1.74 ± 1.70( m, 2 H); 1.59 ± 1.54 (m, 1 H); 1.51 ± 1.42 (m, 4 H); 1.40± 1.20 ( m, 18 H); 1.15 ± 1.11
(m, 2 H); 0.86 (t, J ˆ 6.5, 3 H); 0.63 (m, 2 H); 0.55 (m, 1 H); À0.34 (m, 1 H). 13C-NMR (500 MHz, CDCl3):
81.2; 79.2; 62.1; 31.9; 31.6; 30.2; 29.7 (4 C); 29.4; 29.4; 29.0; 28.7; 28.2; 22.7; 18.8; 15.8; 15.6; 15.5; 14.1; 10.9. HR-
‡
‡
MS (FAB): 321.3152 ([M ‡ H] , C22H40O ; calc. 321.3157).
9-[(1R,2S)-2-Decylcyclopropyl]dec-4-ynal (39). To a soln. of oxalyl chloride (2.56 ml, 28.82 mmol) in
CH2Cl2 (75 ml) at À788 was added dropwise a soln. of DMSO (2.73 ml, 38.43 mmol) in CH2Cl2 (25 ml). The
resulting mixture was stirred at À788 for 30min, and then 38 (6.16 g, 19.22 mmol) in CH2Cl2 (75 ml) was added
dropwise via cannula. The mixture was stirred at À788 for 30min, and then Et 3N (13.39 ml, 96.08 mmol) was
added dropwise, followed by stirring at that temp. for 30min before warming to 25 8 over a period of 30min. The
mixture was diluted with Et2O (250ml) and washed with sat. aq. NH 4Cl soln. (2 Â 75 ml), H2O (75 ml), and
brine (75 ml). The org. layer was dried (MgSO4) and concentrated in vacuo. The resulting oil was then purified
by FC (silica gel; 5% Et2O in hexanes) to afford 39 (5.94 g, 97%). Clear oil. Rf 0.62 (silica gel; 17% AcOEt in
hexanes). [a]D ˆ ‡0.6 (c ˆ 4.0, CHCl3). FT-IR (neat): 2923, 2853, 2719, 1731, 1463, 1410, 1385, 1357, 1332, 1056,
1020, 846, 722. 1H-NMR (500 MHz, CDCl3): 9.78 (t, J ˆ 1.0, 1 H); 2.60 (dt, J ˆ 1.0, 22.5, 2 H); 2.48 ± 2.45
(m, 2 H); 2.12 ± 2.09 (m, 2 H); 1.48 ± 1.43 (m, 4 H); 1.43 ± 1.30( m, 4 H); 1.30± 1.15 ( m, 14 H); 1.15 ± 1.07
(m, 2 H); 0.86 (t, J ˆ 7.0, 3 H); 0.65 ± 0.58 (m, 2 H); 0.57 ± 0.53 (m, 1 H); À0.34 (m, 1 H). 13C-NMR (125 MHz,
CDCl3): 201.1; 81.6; 77.7; 43.0; 31.9; 30.2; 30.1; 29.7; 29.7; 29.6; 29.4; 29.3; 29.8; 28.7; 28.2; 22.7; 22.5; 18.7; 15.7;
‡
‡
15.6; 14.1; 10.9. HR-MS (FAB): ([M ‡ Na] , C22H38NaO ; calc. 341.2820).
10-[1(R,2S)-2-Decylcyclopropyl]dec-1-en-5-yne (40). To a supension of CH2PPh3Br (2.10g, 5.88 mmol) in
THF (40ml) at 0 8 was added NaHMDS soln. (1.0m in THF, 5.14 ml, 5.14 mmol). The mixture was stirred at 08
for 15min before the addition of 39 (1.17 g, 3.67 mmol) in THF (20ml). The mixture was stirred at 0 8 for further
45 min before it was diluted with Et2O (200 ml), and a sat. aq. NH4Cl soln. (75 ml) was added. The layers were
separated, and the org. layer was successively washed with sat. aq. NH4Cl soln. (75 ml), H2O (75 ml), brine
(75 ml), and dried (MgSO4), and concentrated in vacuo. The residue was purified by FC (silica gel; 10% AcOEt
in hexanes) to afford 40 (1.15 g, 97%). Clear oil. Rf 0.73 (silica gel; 10% AcOEt in hexanes). [a]D ˆ ‡0.6 (c ˆ
4.7, CHCl3). FT-IR (neat): 3059, 2923, 2854, 1642, 1463, 1332, 1020, 993, 912, 722. 1H-NMR (400 MHz, CDCl3):
5.87 ± 5.81 (m, 1 H); 5.10± 4.93 ( m, 2 H); 2.22 (d, J ˆ 3.0, 4 H); 2.13 (t, J ˆ 6.5, 2 H); 1.52 ± 1.32 (m, 6 H); 1.28 ±
1.25 (m, 16 H); 1.18 ± 1.09 (m, 2 H); 0.86 (t, J ˆ 6.9, 3 H); 0.64 ± 0.63 (m, 2 H); 0.57 ± 0.53 (m, 1 H); À0.34
(q, J ˆ 4.8, 9.2, 1 H). 13C-NMR (100 MHz, CDCl3): 137.3; 115.3; 80.7; 79.3; 33.4; 31.9; 30.2; 29.7 (3 C); 29.4;
‡
‡
29.4; 29.1; 28.7; 28.2; 22.7; 18.8; 18.7; 15.8; 15.6; 15.5; 14.1; 10.9. GC/MS: 316 (M , C23H40 ; calc. 316).
10-[(1R,2S)-2-Decylcyclopropyl]dec-5-yn-1-ol (41). To a soln. of 40 (0.83 g, 2.63 mmol) in THF (50 ml) at
08 was added dropwise a soln. of 9-BBN (0.5m in THF, 5.50ml, 2.75 mmol) via syringe. The mixture was stirred

1994
Helvetica Chimica Acta ± Vol. 83 (2000)
at 08 for 30min before it was allowed to warm to 25 8 and stirred for an additional 1.5 h. After the mixture was
cooled to 08, sat. aq. NaHCO3 soln. (40ml), and 30% aq. H 2O2 (3 ml) were added. The resulting mixture was
stirred for 1.5 h before a soln. of sat. aq. Na2S2O3 (10ml) was added at 25 8. The mixture was diluted with AcOEt
(100 ml) and washed with H2O (50ml) and brine (50ml). The org. layer was dried (MgSO 4) and concentrated
in vacuo. The crude residue was then purified by FC (silica gel; 10% AcOEt in hexanes) to afford pure 41
(0.74 g, 84%). Waxy solid. Rf 0.29 (silica gel; 17% in hexanes). [a]D ˆ 0.2 (c ˆ 1.8, CHCl3). FT-IR (neat): 3340,
2924, 2854, 1460, 1380, 1334, 1064, 1022, 722. 1H-NMR (500 MHz, CDCl3): 3.66 (t, J ˆ 2 H); 2.20± 2.12 ( m, 4 H);
1.68 ± 1.64 (m, 2 H); 1.58 ± 1.44 (m, 6 H); 1.42 ± 1.18 (m, 19 H); 1.17 ± 1.05 (m, 2 H); 0.87 (t, J ˆ 6.0, 3 H); 0.65 ±
0.60 (m, 2 H); 0.58 ± 0.55 (m, 1 H); À0.34 (m, 1 H). 13C-NMR (125 MHz, CDCl3): 80.7; 79.7; 62.5; 31.9; 31.9;
30.2; 29.7 (4 C); 29.4; 29.3; 29.1; 28.7; 25.3; 22.7; 22.5; 18.8; 18.5; 15.7; 15.6; 14.1; 10.9. HR-MS (MALDI-FT):
‡
‡
357.3141 ([M ‡ Na] , C23H42NaO ; calc. 357.3133).
10-[(1R,2S)-2-Decylcyclopropyl]dec-5-ynal (42). To a soln. of oxalyl chloride (1.95 ml, 21.97 mmol) in
CH2Cl2 (25 ml) at À788 was added dropwise a soln. of DMSO (2.08 ml, 29.29 mmol) in CH2Cl2 (15 ml). The
resulting mixture was stirred at À788 for 30min and then 41 (4.90g, 14.65 mmol) in CH 2Cl2 (15 ml) was added
dropwise via cannula. After stirring at À788 for 30min, Et 3N (10.21 ml, 73.23 mmol) was added dropwise, and
stirring was continued at À788 for 30min before warming to 25 8 over a period of 30min. The mixture was
diluted with Et2O (150ml) and washed with sat. aq. NH 4Cl soln. (2 Â 75 ml), H2O (75 ml), and brine (75 ml).
The org. layer was dried (MgSO4) and concentrated in vacuo. The crude residue was then purified by FC (silica
gel; 5% Et2O in hexanes) to afford 42 (4.74 g, 97%). Clear oil. Rf 0.44 (silica gel; 10% Et2O in hexanes). [a]D
ˆ
0.1 (c ˆ 2.8, CHCl3). FT-IR (neat): 2925, 2854, 2711, 1727, 1459, 1386, 1078, 1020, 722. 1H-NMR (600 MHz,
CDCl3): 9.77 (t, J ˆ 1.3, 1 H); 2.54 (dt, J ˆ 1.4, 7.3, 2 H); 2.24 ± 2.19 (m, 2 H); 1.77 (m, 2 H); 1.49 ± 1.42 (m, 4 H);
1.38 ± 1.15 (m, 20H); 1.15 ± 1.07 ( m, 2 H); 0.86 (t, J ˆ 6.8, 3 H); 0.65 ± 0.60 (m, 2 H); 0.57 ± 0.55 (m, 1 H); À0.34
(m, 1 H). 13C-NMR (150MHz, CDCl 3): 202.1; 81.6; 78.6; 42.8; 31.9; 30.2; 29.7 (3 C); 29.6; 29.4; 29.3; 29.0; 28.7;
‡
‡
28.2; 22.7; 22.5; 18.7; 18.2; 15.7; 15.6; 14.1; 10.9. HR-MS (FAB): 355.2979 ([M ‡ Na] , C23H40NaO ; calc.
355.2977).
Ethyl (E)-12-[(1R,2S)-2-Decylcyclopropyl]dodec-2-en-7-ynoate (43). To a soln. of triethyl phosphono-
acetate (4.22 ml, 16.84 mmol) in THF (75 ml) at 08 was added NaH (0.65 g, 60% in mineral oil, 16.84 mmol).
The resulting mixture was stirred at 08 for 15 min and then cooled to À788 before the dropwise addition of a
soln. of 42 (3.62 g, 10.86 mmol) in THF (50 ml) via syringe. The mixture was stirred at À788 for 30min and then
warmed up to 08 before quenching with aq. NH4Cl soln. (5 ml). The mixture was diluted with Et2O (250ml) and
washed with sat. aq. NH4Cl soln. (100 ml), H2O (75 ml), and brine (75 ml). The org. layer was dried (MgSO4)
and concentrated in vacuo. The crude residue was then purified by FC (silica gel; 5% Et2O in hexanes) to afford
the desired (E)-ester 43 (4.21 g, 96%) and the less-polar undesired (Z)-ester (0.09 g, 2%) as clear oils.
Data of 43: Rf 0.59 (silica gel; 10% Et2O in hexanes). [a]D ˆ À0.2 (c ˆ 2.5, CHCl3). FT-IR (neat): 2925,
2854, 1723, 1655, 1460, 1367, 1318, 1266, 1191, 1151, 1045, 979. 1H-NMR (600 MHz, CDCl3): 6.93 (dt, J ˆ 6.9,
15.6, 1 H); 5.82 (d, J ˆ 15.5, 1 H); 4.16 (q, J ˆ 7.1, 2 H); 2.29 (q, J ˆ 7.0, 2 H); 2.18 ± 2.11 (m,4 H); 1.64 ± 1.59
(m, 2 H); 1.50± 1.39 ( m, 4 H); 1.39 ± 1.15 (m, 21 H); 1.17 ± 1.07 (m, 2 H); 0.85 (t, J ˆ 6.8, 3 H); 0.65 ± 0.60
(m, 2 H); 0.57 ± 0.55 (m, 1 H); À0.34 (m, 1 H). 13C-NMR (150MHz, CDCl 3): 166.8; 148.4; 121.8; 81.2; 79.0;
60.2; 31.9; 31.1; 30.2; 29.7 (4 C); 29.4; 29.4; 29.0; 28.7; 28.2; 27.4; 22.7; 18.8; 18.2; 15.7; 15.6; 14.3; 14.1; 10.9. HR-
‡
‡
MS (FAB): 403.3564 ([M ‡ H] , C27H46O2 ; calc. 403.3576).
Ethyl (2S,3R)-12-[(1R,2S)-2-Decylcyclopropyl]-2,3-dihydroxydodec-7-ynoate (44). To a mixture of tBuOH
(49 ml) and H2O (49 ml) at 258 was added AD-mix b (13.00 g). The resulting mixture was stirred to produce a
biphasic system before it was cooled down to 08. Ester 43 (3.72 g, 9.24 mmol) was added, and the mixture was
stirred at 08 for 8 h. Na2SO3 (13.85 g) was added at 08, and the mixture was allowed to warm to 258 and stirred
further for 40min. The mixture was diluted with AcOEt (250ml), and the aq. layer was extracted further with
AcOEt (2 Â 75 ml). The combined org. layers were extracted wtih 2n aq. KOH soln. (75 ml), dried (MgSO4)
and concentrated in vacuo to give a crude solid, which was purified by FC (silica gel; 20% AcOEt in hexanes) to
afford 44 (2.31 g, 98%). Waxy white solid. M.p. 57 ± 618 (AcOEt). Rf 0.18 (silica gel; 17% AcOEt in hexanes).
[a]D ˆ ‡9.8 (c ˆ ‡1.6, CHCl3). FT-IR (CHCl3 soln.): 3361, 2917, 2851, 1715, 1462, 1386, 1294, 1111, 1069, 720,
1
639. H-NMR (400 MHz, CDCl3): 4.27 (q, J ˆ 7.1, 2 H); 4.06 (dd, J ˆ 2.1, 5.1, 1 H); 3.93 ± 3.87 (m, 1 H); 2.22 ±
2.11 (m, 4 H); 1.90± 1.83 ( m, 1 H); 1.74 ± 1.41 (m, 9 H); 1.40± 1.20 ( m, 21 H); 1.15 ± 1.07 (m, 2 H); 0.86 (t, J ˆ
6.4, 3 H); 0.65 ± 0.58 (m, 2 H); 0.57 ± 0.52 (m, 1 H); À0.34 (m, 1 H). 13C-NMR (100 MHz, CDCl3): 172.1; 80.9;
79.5; 73.1; 72.1; 62.2; 32.9; 31.9; 30.2; 29.7 (4 C); 29.4; 29.4; 29.1; 28.7; 28.2; 25.3; 22.7; 18.8; 18.6; 15.7; 15.6; 14.1;
‡
‡
14.1; 10.9. HR-MS (FAB): 459.3463 ([M ‡ Na] , C27H48NaO4 ; calc. 459.3450).
Ethyl (2S,3R,7Z)-12-[(2R,3S)-2-Decylcyclopropyl]-2,3-dihydroxydodec-7-enoate (45). A mixture of 44
(1.51 g, 3.46 mmol) and Lindlar catalyst (180mg) in EtOH (75 ml) was stirred under 1 atm H 2 at 258 for 40min.

Helvetica Chimica Acta ± Vol. 83 (2000)
1995
The catalyst was filtered off through a pad of Celite and rinsed with AcOEt (25 ml). The filtrate was
concentrated in vacuo to afford 45 (1.51 g, 100%). Waxy white solid. M.p. 56 ± 608 (AcOEt). Rf 0.39 (silica gel;
10% Et2O in hexanes). [a]D ˆ ‡6.7 (c ˆ 1.2, CHCl3). FT-IR (CHCl3 soln.): 3416, 2925, 2860, 1737, 1455, 1273,
1208, 1084, 1038. 1H-NMR (600 MHz, CDCl3): 5.40± 5.32 ( m, 2 H); 4.27 (q, J ˆ 7.2, 2 H); 4.05 (d, J ˆ 5.0, 1 H);
3.87 (q, J ˆ 7.6, 1 H); 3.01 (d, J ˆ 5.1, 1 H); 2.07 (q, J ˆ 7.3, 2 H); 2.03 ± 1.95 (m, 3 H); 1.84 (d, J ˆ 9.2, 1 H); 1.63 ±
1.51 (m, 3 H); 1.45 ± 1.15 (m, 25 H); 1.15 ± 1.07 (m, 2 H); 0.86 (t, J ˆ 6.8, 3 H); 0.65 ± 0.60 (m, 2 H); 0.60 ± 0.55
(m, 1 H); À0.35 (m, 1 H). 13C-NMR (150MHz, CDCl 3): 173.6; 130.6; 129.0; 73.0; 72.4; 62.2; 33.4; 31.9; 30.2;
29.9; 29.7 (4 C); 29.6; 29.4; 28.7; 28.6; 27.3; 26.9; 25.8; 22.7; 15.8; 15.7; 14.2; 14.1; 10.9. HR-MS (FAB): 461.3605
‡
‡
([M ‡ Na] , C27H50NaO4 ; calc. 461.3607).
Ethyl
(2S,3R,7Z)-12-[(1R,2S)-2-Decylcyclopropyl]-3-hydroxy-2-[(4-nitrophenylsulfonyl)oxy]dodec-7-
enoate (46). To a soln. of 45 (0.94 g, 2.14 mmol) in pyridine (45 ml) at 08 was added 4-nitrobenzenesulfonyl
chloride (0.61 g, 2.46 mmol) in one portion. The resulting mixture was stirred at 08 for 6.5 h before it was
quenched with icy cold H2O (2 ml). The mixture was diluted with cold Et2O (200 ml) and extracted with cold sat.
aq. CuSO2, soln. (50ml), cold H 2O (2 Â 100 ml), and cold brine (100 ml). The org. layer was dried (MgSO4) and
concentrated in vacuo (below 108). The oily residue was purified by FC (silica gel; 12% chilled AcOEt in
hexanes) to afford 46 (1.12 g, 84%) as a clear oil which solidified to a white solid upon standing. Rf 0.53 (silica
gel; 25% AcOEt in hexanes). [a]D ˆ ‡2.5 (c ˆ 1.7, CHCl3). FT-IR (neat): 3436, 2925, 2855, 1750, 1534, 1354,
1188, 1102, 1025, 855. 1H-NMR (600 MHz, CDCl3): 8.38 (d, J ˆ 8.2, 2 H); 8.16 (d, J ˆ 8.0, 2 H); 5.41 ± 5.27
(m, 2 H); 4.97 (d, J ˆ 2.4, 1 H); 4.15 (q, J ˆ 7.1, 2 H); 4.10± 4.07 ( m, 1 H); 2.07 ± 1.99 (m, 4 H); 1.76 (d, J ˆ 8.4,
1 H); 1.60± 1.50( m, 4 H); 1.45 ± 1.15 (m, 25 H); 1.15 ± 1.07 (m, 1 H); 0.86 (t, J ˆ 7.0, 3 H); 0.65 ± 0.60 (m, 2 H);
0.55 ± 0.52 (m, 1 H); À0.34 (m, 1 H). 13C-NMR (150MHz, CDCl 3): 166.7; 151.0; 142.0; 137.8; 131.0; 129.5;
129.5; 128.5; 124.2; 124.2; 80.9; 71.6; 62.4; 32.7; 31.9; 30.2; 29.9; 29.7 (4 C); 29.4; 28.7; 28.6; 27.4; 26.7; 25.3; 22.7;
‡
‡
15.8; 15.7; 14.1; 14.0; 10.9. HR-MS (FAB): 646.3402 ([M ‡ Na] , C33H53NNaO8S ; calc. 646.3384).
Ethyl (2R,3R,7Z)-2-Azido-12-[(1R,2S)-2-decylcyclopropyl]-3-hydroxydodec-7-enoate (47). A mixture of
46 (0.88 g, 1.41 mmol) and NaN3 (0.23 g, 3.54 mmol) in DMF (8 ml) was stirred at 258 for 36 h. The mixture was
diluted with Et2O (25 ml) and washed with H2O (2 Â 10ml), and brine (100ml). The org. layer was dried
(MgSO4) and concentrated in vacuo. The crude residue was purified by FC (silica gel; 20% Et2O in hexanes) to
afford 47 (0.62 g, 95%). Clear oil. Rf 0.53 (silica gel; 25% AcOEt in hexanes). [a]D ˆ ‡3.4 (c ˆ 0.9, CHCl3). FT-
IR (neat): 3401, 2925, 2849, 2107, 1743, 1455, 1378, 1261, 1190, 1085, 1026. 1H-NMR (500 MHz, CDCl3): 5.53 ±
5.30( m, 2 H); 4.32 ± 4.23 (m, 2 H); 3.93 ± 3.88 (m, 2 H); 2.26 ± 2.22 (m, 1 H); 2.10± 1.95 ( m, 4 H); 1.60± 1.45
(m, 3 H); 1.45 ± 1.15 (m, 26 H); 1.15 ± 1.07 (m, 2 H); 0.86 (t, J ˆ 7.1, 3 H); 0.65 ± 0.58 (m, 2 H); 0.55 ± 0.50
(m, 1 H); À0.35 (m, 1 H). 13C-NMR (125 MHz, CDCl3): 169.0; 129.8; 128.9; 71.9; 66.2; 62.1; 32.6; 32.0; 30.2;
29.9; 29.7 (4 C); 29.6; 29.4; 28.7; 28.6; 27.3; 26.9; 25.5; 22.7; 15.8; 15.7; 14.2; 14.1; 10.9. HR-MS (MALDI-FT):
‡
‡
‡
‡
436.3810([ M‡ HÀ N2] , C27H49NO3 ; calc. 436.3791). LS-MS (ESI): 486 [M‡ Na ], C27H49N3NaO3 ; calc. 486).
Ethyl (2R,3R,7Z)-2-Azido-3-[(tert-butyl)dimethylsilyloxy]-12-[(1R,2S)-2-decylcyclopropyl]dodec-7-
enoate (48). To a stirred soln. of 47 (0.63 g, 1.36 mmol) and 2,6-lutidine (0.40 ml, 3.40 mmol) in CH2Cl2
(15 ml) at À788 was added dropwise TBDMSOTf (0.31 ml, 1.43 mmol) via syringe. The mixture was allowed to
warm to 258 and stirred further for 25 min before it was diluted with Et2O (25 ml) and extracted successively
with aq. CuSO4 soln. (5 ml), H2O (10ml), and brine (5 ml). The org. layer was dried (MgSO 4) and concentrated
in vacuo to afford 48 (0.79 g, 100%). Faintly yellow oil. Rf 0.68 (silica gel; 10% AcOEt in hexanes). [a]D ˆ À7.6
(c ˆ 0.5, CHCl3). FT-IR (neat): 2927, 2860, 2108, 1725, 1455, 1378, 1255, 1184, 1108, 1026, 837. 1H-NMR
(500 MHz, CDCl3): 5.39 ± 5.29 (m, 2 H); 4.21 (q, J ˆ 7.0, 2 H); 4.07 (td, J ˆ 1.4, 4.8, 1 H); 3.93 (d, J ˆ 5.0, 1 H);
2.04 ± 1.95 (m, 4 H); 1.69 ± 1.62 (m, 1 H); 1.52 ± 1.48 (m, 1 H); 1.47 ± 1.15 (m, 27 H); 1.15 ± 1.07 (m, 2 H); 0.87 ±
0.84 (m, 12 H); 0.65 ± 0.58 (m, 2 H); 0.55 ± 0.50 (m, 1 H); 0 .0 7 s(, 6 H); À0.35 (m, 1 H). 13C-NMR (125 MHz,
CDCl3): 169.0; 130.6; 128.9; 73.1; 66.2; 61.7; 32.7; 31.9; 30.2; 29.9; 29.7 (5 C); 29.6; 29.4; 28.7; 28.6; 27.5; 27.1;
25.7; 25.7; 25.7; 24.6; 22.7; 18.0; 15.8; 15.7; 14.1; 10.9; À4.5; À4.7. HR-MS (MALDI-FT): 550.4633 ([M ‡ H À
‡
‡
‡
‡
N2] , C33H63NO3Si ; calc. 550.4655) LS-MS (ESI): 601 ([M ‡ Na] , C33H63NaN3O3Si ; calc. 601).
(2S,3R,7Z)-2-Azido-3-[(tert-butyl)dimethylsilyloxy]-12-[(1R,2S)-2-decylcyclopropyl]dodec-7-en-1-ol
(14). To a stirred soln. of 48 (0.77 g, 1.33 mmol) in THF (25 ml) at 08 was added dropwise a soln. of LiBH4 (2.0m
in THF, 1.66 ml, 3.32 mmol) via syringe. The mixture was stirred at 08 for 10h before it was quenched carefully
with MeOH (1 ml), diluted with AcOEt (10ml) and washed successively with H 2O (5 ml) and brine (5 ml). The
org. layer was dried (MgSO4) and concentrated in vacuo. The residue was then purified by FC (silica gel; 17%
AcOEt in hexanes) to afford 14 (0.63 g, 92%). Faintly yellow oil. Rf 0.39 (silica gel; AcOEt/hexanes 1:5).
[a]D ˆ À7.1 (c ˆ 1.1, CHCl3). FT-IR (neat). 3381, 2925, 2860, 2101, 1464, 1367, 1256, 1083, 1044, 836, 777.
1H-NMR (500 MHz, CDCl3): 5.47 ± 5.28 (m, 2 H); 3.82 ± 3.68 (m, 3 H); 3.50± 3.45 ( m, 1 H); 2.26 (br. s, OH);
2.05 ± 1.97 (m, 4 H); 1.69 ± 1.60( m, 1 H); 1.50± 1.44 ( m, 2 H); 1.39 ± 1.18 (m, 23 H); 1.18 ± 1.07 (m, 2 H); 0.89 ±

1996
Helvetica Chimica Acta ± Vol. 83 (2000)
0.84 (m, 12 H); 0.65 ± 0.58 (m, 2 H); 0.55 ± 0.50 (m, 1 H); 0 .10 s(, 3 H); 0 .0 7s(, 3 H); À0.35 (m, 1 H). 13C-NMR
(125 MHz, CDCl3): 130.7; 128.9; 73.1; 66.7; 62.2; 33.4; 31.9; 31.9; 30.2; 29.7 (3 C); 29.6; 29.4; 28.7; 28.6; 27.3; 27.2;
25.8; 25.8; 25.8; 24.8; 24.9; 22.7; 18.0; 15.7; 15.7; 14.1; 10.9; À4.6; À4.7. HR-MS (MALDI-FT): 508.4558 ([M ‡
‡
‡
H À N2] , C31H61NO2Si ; calc. 508.4550). LR-MS (ESI): 571 ([M ‡ Cl]À, C31H61ClN3O2SiÀ; calc. 571).
(2R)-12-[(1R,2S)-2-Decylcyclopropyl]dodec-7-yne-1,2-diol (49): To
a stirred biphasic mixture of
K3Fe(CN)6 (9.42 g, 28.60mmol), K 2CO3 (4.00 g, 28.57 mmol), K2Os2(OH)4 (13.3 g, 0.04 mmol), and
(DHQD)2AQN (9.42 mg, 0.09 mmol) in tBuOH (45 ml) and H2O (45 ml) at 08 was added 40 (3.01 g,
9.52 mmol). The flask containing the olefin was rinsed with tBuOH (1.5 ml) and H2O (1.5 ml), and the rinse was
then added to the mixture, and stirring was continued at 08 for 8 h. The mixture was quenched by addition of
Na2SO3 (7.62 g) at 08 before it was allowed to warm to 258 over 30min. The two phases were separated, and the
aqueous layer was further extracted with AcOEt (2 Â 75 ml). The combined org. layers were successively
washed with H2O (75 ml), brine (75 ml), dried (MgSO4) and concentrated in vacuo. The residue was purified by
FC (silica gel; 10% acetone in CH2Cl2) to afford 49 (3.04 g, 91%). White solid. M.p. 84 ± 858 (AcOEt). Rf 0.13
(silica gel, 20% AcOEt in hexanes). [a]D ˆ ‡3.9 (c ˆ 1.0, CHCl3). FT-IR (CHCl3 soln.): 3379, 2924, 2854, 1458,
1377, 1091, 1044. 1H-NMR (400 MHz, CDCl3): 3.89 ± 3.84 (m, 1 H); 3.68 ± 3.62 (m, 1 H); 3.50± 3.44 ( m, 1 H);
2.42 (d, J ˆ 4.0, 1 H); 2.32 ± 2.30 (m, 2 H); 2.14 ± 2.11 (m, 2 H); 1.99 (t, J ˆ 5.6, 1 H); 1.65 ± 1.58 (m, 2 H); 1.51 ±
1.40( m, 4 H); 1.35 ± 1.24 (m, 18 H); 1.15 ± 1.10( m, 2 H); 0.86 (t, J ˆ 6.8, 3 H); 0.64 ± 0.63 (m, 2 H); 0.57 ± 0.52
(m, 1 H); À0.34 (m, 1 H). 13C-NMR (100 MHz, CDCl3): 81.5; 79.1; 71.5; 66.6; 32.0; 31.9; 30.2; 29.7 (3 C); 29.4;
‡
‡
29.4; 29.0; 28.7; 28.2; 22.7; 18.7; 18.7; 15.7; 15.6; 15.2; 14.1; 10.9. HR-MS (FAB): 351.3257 ([ M ‡ H] , C23H42O2
;
calc. 351.3263).
(2R)-10-[(1R,2S)-2-Decylcyclopropyl]-2-hydroxydec-5-ynyl 2,2,2-Trimethylethanoate (50). To a stirred
soln. of 49 (1.90g, 5.41 mmol) in pyridine (15 ml) at 0 8 was added freshly distilled pivaloyl chloride (0.67 ml,
5.42 mmol). The mixture was stirred at 258 for 40min before it was quenched by the addition of cold H 2O
(0.5 ml). The mixture was diluted with Et2O (75 ml) and successively washed with sat. aq. NaHCO3 soln. (2 Â
50ml), 1n aq. HCl soln. (2 Â 50ml), H 2O (50ml), and brine (50ml). The org. layer was dried (MgSO 4) and
concentrated in vacuo. The residue was then purified by FC (silica gel; 10% AcOEt in hexanes) to afford 47
(2.14 g, 91%). Faintly yellow oil. Rf 0.57 (silica gel; 25% AcOEt in hexanes). [a]D ˆ ‡1.4 (c ˆ 2.7, CHCl3). FT-
IR (neat): 3478, 3058, 2921, 2853, 1738, 1715, 1455, 1285, 1158, 1107. 1H-NMR (500 MHz, CDCl3): 4.11 (dd, J ˆ
2.9, 10.6, 1 H); 4.01 ± 3.97 (m, 2 H); 2.33 ± 2.30( m, 2 H); 2.14 ± 2.11 (m, 2 H); 1.66 ± 1.62 (m, 2 H); 1.51 ± 1.34
(m, 8 H); 1.30± 1.20 ( m, 24 H); 1.16 ± 1.07 (m, 2 H); 0.86 (t, J ˆ 7.0, 3 H); 0.66 ± 0.60 (m, 2 H); 0.57 ± 0.52
(m, 1 H); À0.34 (m, 1 H). 13C-NMR (125 MHz, CDCl3): 178.7; 81.4; 79.0; 69.3; 68.2; 38.9; 32.5; 31.9; 30.2; 29.7;
29.7; 29.7; 29.6; 29.4; 29.4; 29.0; 28.7; 28.2; 27.2 (3 C); 22.7; 18.8; 15.8; 15.6; 15.1; 14.1; 10.9. HR-MS (FAB):
‡
‡
435.3844 ([M ‡ H] , C28H50O3 ; calc. 435.3838).
(2R)-2-[(tert-Butyl)dimethylsilyloxy]-10-[(1R,2S)-2-decylcyclopropyl]dec-5-ynyl 2,2,2-Trimethylethanoate
(51). To a stirred soln. of 50 (1.32 g, 3.03 mmol) and 2,6-lutidine (0.88 ml, 7.57 mmol) in CH2Cl2 (15 ml) at À788
was added dropwise TBDMSOTf (0.65 ml, 3.06 mmol) via syringe. The mixture was allowed to warm to 258 and
stirred further for 15 min before it was diluted with Et2O (50ml) and successively extracted with aq. CuSO 4 soln.
(15 ml), H2O (20ml), and brine (15 ml). The org. layer was dried (MgSO 4) and concentrated in vacuo to afford
51 (1.67 g, 100%). Faintly yellow oil. Rf 0.85 (silica gel; 17% Et2O in hexanes). [a]D ˆ ‡5.2 (c ˆ 1.6, CHCl3). FT-
IR (neat): 2926, 2855, 1738, 1734, 1462, 1283, 1354, 1154, 1121, 1018, 837, 777. 1H-NMR (500 MHz, CDCl3):
3.99 ± 3.93 (m, 3 H); 2.23 ± 2.20( m, 2 H); 2.13 ± 2.11 (m, 2 H); 1.65 ± 1.63 (m, 2 H); 1.51 ± 1.30( m, 8 H); 1.30±
1.20( m, 14 H); 1.18 (s, 9 H); 1.16 ± 1.07 (m, 2 H); 0.90 ± 0.86 (m, 12 H); 0.66 ± 0.60 (m, 2 H); 0.57 ± 0.53
(m, 1 H); 0 .0 8s(, 3 H); 0 .0 7s(, 3 H); À0.34 (m, 1 H). 13C-NMR (125 MHz, CDCl3): 178.3; 80.8; 79.4; 68.7; 67.8;
38.8; 33.9; 31.9; 30.2; 29.7; 29.7; 29.7; 29.7; 29.4; 29.3; 29.0; 28.7; 28.2; 27.2 (3 C); 25.7 (3 C); 22.7; 18.8; 18.1; 15.7;
‡
‡
15.6; 14.7; 14.1; 10.9; À4.6; À4.8. HR-MS (FAB): 571.4509 ([M ‡ Na] , C34H64NaO3Si ; calc. 571.4522).
(2R)-2-[(tert-Butyl)dimethylsilyloxy]-10-[(1R,2S)-2-decylcyclopropyl]dec-5-yn-1-ol (52). To stirred
a
soln. of 51 (1.65 g, 3.01 mmol) in CH2Cl2 (20ml) at À788 was added dropwise a soln. of DIBAL (1.0m in
CH2Cl2, 0.68 ml, 3.19 mmol). The mixture was stirred at À788 for 20min before it was quenched with MeOH
(0.1 ml) and allowed to warm to 258. AcOEt (25 ml) and sat. aq. soln. of Rochelleꢀs salt (5 ml) were added, and
the resulting cloudy mixture was stirred further at 258 until it became clear (30min). The org. layer was further
washed with H2O (2 ml), brine (2 ml), dried (MgSO4), and concentrated in vacuo to give the crude product as a
viscous oil. The crude product was then purified by FC (silica gel; 10% AcOEt in hexanes) to afford 52 (1.40g,
100%). Clear oil. Rf 0.47 (silica gel; 17% AcOEt in hexanes). [a]D ˆ ‡0.1 (c ˆ 1.0, CHCl3). FT-IR (neat): 3384,
2925, 2855, 1463, 1386, 1254, 1113, 1048, 837, 777. 1H-NMR (500 MHz, CDCl3): 3.93 ± 3.88 (m, 1 H); 3.60( d, J ˆ
11, 1 H); 3.49 ± 3.45 (m, 1 H); 2.20± 2.16 ( m, 4 H); 1.86 (br. s, 1 H); 1.72 ± 1.62 (m, 2 H); 1.51 ± 1.32 (m, 8 H);

Helvetica Chimica Acta ± Vol. 83 (2000)
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1.31 ± 1.20( m, 14 H); 1.16 ± 1.07 (m, 2 H); 0.90 ± 0.86 (m, 12 H); 0.66 ± 0.60 (m, 2 H); 0.57 ± 0.53 (m, 1 H); 0.10
(s, 3 H); 0 .0 9s(, 3 H); À0.34 (m, 1 H). 13C-NMR ( 125MHz, CDCl3): 80.9; 79.3; 71.4; 66.1; 33.8; 31.9; 30.2; 29.7;
29.7; 29.7; 29.7; 29.4; 29.3; 29.0; 28.7; 28.2; 25.8 (3 C); 22.7; 18.8; 18.1; 15.7; 15.6; 14.8; 14.1; 10.9; À4.6; À4.6.
‡
‡
HR-MS (FAB): 465.4115 ([M ‡ H] , C29H56O2Si ; calc. 465.4128).
(2R,5Z)-2-[(tert-Butyl)dimethylsilyloxy]-10-[(1R,2S)-2-decylcyclopropyl]dec-5-en-1-ol (53). A mixture of
52 (1.40g, 3.01 mmol) and Lindlar catalyst (150mg) in EtOH (75 ml) under 1 atm H 2 at 258 was stirred for
30min. The catalyst was removed by filtering through a pad of Celite and rinsing with AcOEt (25 ml). The
filtrate was concentrated in vacuo to give pure 53 (1.40 g, 100%). Viscous oil. Rf 0.47 (silica gel; 12% AcOEt in
hexanes). [a]D ˆ ‡0.1 (c ˆ 1.7, CHCl3). FT-IR (neat): 3421, 2926, 2855, 1463, 1383, 1254, 1107, 1046, 836, 777.
1H-NMR (600 MHz, CDCl3): 5.39 ± 5.31 (m, 2 H); 3.75 ± 3.71 (m, 1 H); 3.57 ± 3.53 (m, 1 H); 3.45 (dd, J ˆ 5.4,
11.1, 1 H); 2.10± 1.96 ( m, 4 H); 1.85 (br. s, 1 H); 1.58 ± 1.50( m, 2 H); 1.36 ± 1.30( m, 8 H); 1.31 ± 1.18 (m, 14 H);
1.16 ± 1.07 (m, 2 H); 0.90 ± 0.86 (m, 12 H); 0.66 ± 0.60 (m, 2 H); 0.57 ± 0.53 (m, 1 H); 0 .0 7 s(, 3 H); 0 .0 7 s(, 3 H);
À0.35 (m, 1 H). 13C-NMR (150MHz, CDCl 3): 130.5; 128.8; 72.5; 66.1; 34.0; 31.9; 30.2; 29.9; 29.7; 29.7; 29.7;
29.7; 29.7; 29.4; 28.7; 28.6; 27.3; 25.8 (3 C); 23.2; 22.7; 18.1; 15.8; 15.7; 14.1; 10.9; À4.5; À4.6. HR-MS (FAB):
‡
‡
457.4299 ([M ‡ H] , C29H58O2Si ; calc. 467.4287).
(2R,5Z)-2-[(tert-Butyl)dimethylsilyloxy]-10-[(1R,2S)-2-decylcyclopropyl]dec-5-enal (54). To a soln. of 53
(1.40g, 3.01 mmol) in CH 2Cl2 (25 ml) at 08 was added Dess-Martin periodinane reagent (1.50g, 3.61 mmol). The
mixture was allowed to warm to 258 and stirred further for 40min. A soln. of Na 2S2O3 (20% in sat. NaHCO3,
5 ml) was added, and the resulting cloudy mixture was stirred at 258 until it became clear (30min). The layers
were separated, and the org. layer was washed with H2O (10ml), brine (10ml), dried (MgSO 4), and
concentrated in vacuo. The crude product was then purified by FC (silica gel; 10% Et2O in hexanes) to give 54
(1.34 g, 96%). Clear oil. Rf 0.59 (silica gel; 10% Et2O in hexanes). [a]D ˆ ‡7.1 (c ˆ 0.9, CHCl3). FT-IR (neat):
2925, 2854, 1738, 1464, 1376, 1255, 1112, 1020, 837, 779. 1H-NMR (600 MHz, CDCl3): 9.58 (d, J ˆ 1.6, 1 H); 5.43 ±
5.28 (m, 2 H); 3.98 ± 3.96 (m, 1 H); 2.20± 2.14 ( m, 1 H); 2.10± 2.00 ( m, 3 H); 1.72 ± 1.62 (m, 2 H); 1.36 ± 1.30
(m, 8 H); 1.31 ± 1.18 (m, 14 H); 1.16 ± 1.07 (m, 2 H); 0.91 (s, 9 H); 0.86 (t, J ˆ 7.1, 3 H); 0.66 ± 0.60 (m, 2 H);
0.56 ± 0.53 (m, 1 H); 0 .0 7 s(, 3 H); 0 .0 6 s(, 3 H); À0.35 (m, 1 H). 13C-NMR (150MHz, CDCl 3): 204.3; 131.4;
128.2; 77.3; 33.0; 31.9; 30.2; 30.0; 29.7; 29.7; 29.7; 29.7; 29.6; 29.4; 28.7; 28.6; 27.3; 25.7 (3 C); 23.2; 22.7; 18.2; 15.8;
‡
‡
15.7; 14.1; 10.9; À4.6; À4.9. HR-MS (FAB): ([M ‡ Na] , C29H56NaO2Si ; calc. 487.3947).
(2R,5Z)-2-[(tert-Butyl)dimethylsilyloxy]-10-[(1R,2S)-2-decylcyclopropyl]dec-5-enoic Acid (12). To
mixture of 54 (0.80 g, 1.73 mmol) and 2-methylbut-2-ene (2.0m in THF, 17.29 ml, 34.8 mmol) in tBuOH
a
(68 ml) and H2O (14 ml) at 08 was added NaH2PO4(3.60g, 20.70mmol), followed by NaClO
(0.39 g,
2
4.32 mmol) in small portions. The slightly yellowish mixture was stirred at 08 for 30min before a sat. soln. of
Na2S2O3 in pH 7 phosphate buffer (3 ml) was added to the mixture. The mixture was extracted with AcOEt (3 Â
75 ml), and the combined org. layers were washed with sat. aq. NH4Cl soln. (20ml), H 2O (20ml), brine (20ml),
dried (MgSO4), and concentrated in vacuo to afford 12 (> 95%) as a waxy solid, which was used in the following
step without further purification. For characterization purposes, a small amount of crude product was purified by
FC (silica gel; 50% AcOEt in hexanes to 50% AcOEt in CH2Cl2) to give pure 12 and a small amount of a-(tert-
Butyl)dimethylsilyloxy acid 12a.
‡
‡
Data of 12: HR-MS (FAB): 411.2846 ([M ‡ H ‡ 2 Na] , C23H42Na2O3 ; calc. 411.2851).
Data of 12a: Rf 0.12 (silica gel; 25% AcOEt in hexanes). [a]D ˆ ‡0.8 (c ˆ 0.8, CHCl3). FT-IR (neat): 3383,
2924, 2854, 1730, 1459, 1279, 1088, 742. 1H-NMR (500 MHz, CDCl3): 9.50(br. s, OH); 5.41 ± 5.29 (m, 2 H); 4.28
(t, J ˆ 5.5, 1 H); 2.18 ± 1.95 (m, 4 H); 1.87 ± 1.72 (m, 2 H); 1.36 ± 1.30( m, 8 H); 1.31 ± 1.18 (m, 14 H); 1.16 ± 1.07
(m, 2 H); 0.92 (s, 9 H); 0.86 (t, J ˆ 7.5, 3 H); 0.66 ± 0.60 (m, 2 H); 0.56 ± 0.53 (m, 1 H); 0.12 (s, 3 H); 0.12 (s, 3 H);
À0.35 (m, 1 H). 13C-NMR (125 MHz, CDCl3): 174.2; 131.4; 127.6; 71.8; 34.7; 31.9; 30.2; 29.9; 29.7; 29.7; 29.7;
29.7; 29.7; 29.4; 28.7; 28.6; 27.3; 25.6 (3 C); 22.7; 22.1; 18.1; 15.8; 15.7; 14.1; 10.9; À4.9; À5.3. HR-MS (FAB):
‡
‡
503.3878 ([M ‡ Na] , C29H56NaO3Si ); calc. 503.3896).
(2S,3R)-2-Azido-3-[(tert-Butyl)dimethylsilyloxy]-1-{6-O-[(tert-butyl)diphenylsilyl]-3,4-O-isopropylidene-
2-O-(trimethylacetyl)-b-d-galactopyranosyloxy}-10-[(1R,2S)-2-decylcyclopropyl]decane (55). The following
protocol was followed prior to the glycosidation reaction. The mixture of glycosyl acceptor and donor was
azeotroped with dry benzene (3 Â 5 ml) in a dried flask and placed under vacuum for 1 h before the reaction.
The glycosidation catalysts (AgOTf and SnCl2) were added to a dried flask with a magnetic stirring bar. The
mixture in the flask wrapped in Al foil was azeotroped with dry benzene (2  5 ml) in the dark. Activated 4-Š
molecular sieves were added to the flask, and the mixture was azeotroped with benzene once more (5 ml) before
placed under vacuum for 1 h.
To a stirred mixture of AgOTf (83 mg, 323 mmol), SnCl2(61 mg, 323 mmol), and 4-Š molecular sieves
(200 mg) in dry CH2Cl2 (3 ml) under Ar at 08 was added a soln. of 13 (65 mg, 129 mmol) and 11 (106 mg,

1998
Helvetica Chimica Acta ± Vol. 83 (2000)
194 mmol) in dry CH2Cl2 (3 ml) via syringe. To the mixture was then added 2,6-di(tert-butyl)-4-methylpyridine
(32 mg, 155 mmol) in one portion. The mixture was then stirred at 08 in the dark for 3 h before it was allowed to
warm to 258 and stirred further for 3.5 h. The mixture was diluted with AcOEt (12 ml), filtered through a pad of
Celite, and rinsed with AcOEt (10ml). The org. filtrate was washed with sat. aq. NaHCO 3 soln. (2 Â 5 ml), H2O
(7 ml), and brine (7 ml). The org. extract was dried (MgSO4) and concentrated in vacuo to a crude oil, which
was then purified by FC (silica gel; 5% AcOEt in hexanes) to afford 55 (125 mg, 93%). Clear oil. Rf 0.52 (silica
gel; 10% AcOEt in hexanes). [a]D ˆ ‡3.7 (c ˆ 2.6, CHCl3). FT-IR (neat): 2929, 2855, 2099, 1741, 1464, 1377,
1255, 1137, 1112, 1080, 833, 704. 1H-NMR (600 MHz, CDCl3): 7.70± 7.66 ( m, 4 arom. H); 7.43 ± 7.34
(m, 6 arom. H); 4.94 (t, J ˆ 6.0, HÀC(2')); 4.33 (d, J ˆ 8.1, HÀC(1')); 4.29 (dd, J ˆ 1.9, 5.3, HÀC(4')); 4.14
(dd, J ˆ 5.4, 7.2, HÀC(3')); 3.97 (dd, J ˆ 7.5, 9.7, 1 HÀC(6')); 3.91 (dd, J ˆ 6.0, 9.7, 1 HÀC(6')); 3.87 ± 3.85
(m, HÀC(5')); 3.78 (dd, J ˆ 8.3, 11.7, 1 HÀC(1)); 3.73 ± 3.70( m, HÀC(3)); 3.54 ± 3.51 (m, 1 HÀC(1), HÀC(2));
1.56 ± 1.50( m, 4 H); 1.35 ± 1.18 (m, 41 H); 1.15 ± 1.05 (m, 2 H); 1.0 4 (s, 9 H); 0.87 ± 0.85 (m, 12 H); 0.65 ± 0.63
(m, 2 H); 0.57 ± 0.53 (m, 1 H); 0 .0 2s(, 6 H); À0.35 (m, 1 H). 13C-NMR (150MHz, CDCl 3): 176.8; 135.6; 135.6;
135.5; 135.5; 133.3; 133.2; 129.8; 129.7; 127.7; 127.7; 127.6; 127.6; 110.3; 100.0; 73.4; 73.2; 72.7; 72.1; 67.9; 65.3;
62.5; 32.8; 31.9; 30.2; 29.8; 29.7; 29.7; 29.7; 29.7; 29.7; 29.6; 29.6; 29.4; 28.7; 28.7; 28.7; 28.7; 27.7; 27.1; 27.1; 26.7;
26.7; 26.7; 26.4; 25.8; 25.8; 25.8; 24.8; 24.7; 22.7; 19.2; 18.0; 15.7; 15.7; 14.1; 10.9; À4.6; À4.6; HR-MS (MALDI-
‡
‡
FT): 1056.6874 ([M ‡ Na] , C59H99N3NaO8Si2 ; calc. 1056.6868).
(2S,3R)-2-Azido-3-[(tert-butyl)dimethylsilyloxy]-1-{6-O[(tert-butyl)diphenylsilyl]-3,4-O-isopropylidene-b-d-
galactopyranosyloxy}-10-[(1R,2S)-2-decylcyclopropyl]decane (56). To a soln. of 55 (69 mg, 67 mmol) in dry
CH2Cl2 (1.5 ml) at À788 was added dropwise a soln. of DIBAL (1.0m in CH2Cl2, 133 ml, 133 mmol). The mixture
was stirred at À788 for 15 min before it was quenched by the addition of MeOH (100 ml), diluted with AcOEt
(5 ml) and allowed to warm to 258. Sat. aq. soln. of Rochelleꢀs salt (1.5 ml) was added, and the resulting cloudy
mixture was stirred further until it became clear (30min). The org. layer was further washed with H 2O (2 ml),
brine (2 ml), dried (MgSO4), and concentrated in vacuo. The crude product was purified by FC (silica gel; 12%
AcOEt in hexanes) to afford 56 (62 mg, 98%). Clear oil. Rf 0.18 (silica gel; 10% AcOEt in hexanes). [a]D
ˆ
‡1.3 (c ˆ 3.0, CHCl3). FT-IR (neat): 3424, 2927, 2855, 2099, 1462, 1380, 1253, 1110, 834, 703. 1H-NMR
(600 MHz, CDCl3): 7.70± 7.66 ( m, 4 arom. H); 7.44 ± 7.32 (m, 6 arom. H); 4.28 (dd, J ˆ 1.4, 5.3, HÀC(4')); 4.15
(d, J ˆ 8.2, HÀC(1')); 4.06 (t, J ˆ 6.9, HÀC(3')); 3.97 (dd, J ˆ 7.7, 9.5, HÀC(6')); 3.92 ± 3.87 (m, 1 HÀC(1),
HÀC(5'), 1 HÀC(6')); 3.85 (t, J ˆ 7.3, HÀC(5')); 3.73 (dd, J ˆ 4.7, 9.3, HÀC(3)); 3.65 (dd, J ˆ 3.9, 10.7,
1 HÀC(1)); 3.58 ± 3.53 (m, HÀC(2), HÀC(2')); 2.40( d, J ˆ 2.0, 1 H); 1.60 ± 1.56 (m, 1 H); 1.50( s, 3 H); 1.41 ±
1.21 (32 H); 1.15 ± 1.09 (m, 2 H); 1.0 4 (s, 9 H); 0.87 (t, J ˆ 6.7, 3 H); 0.84 (s, 9 H); 0.65 ± 0.60 (m, 2 H); 0.57 ± 0.53
(m, 1 H); 0 .0 3 s(, 3 H); 0 .0 2 s(, 3 H); À0.34 (m, 1 H). 13C-NMR (100 MHz, CDCl3): 135.6; 135.6; 135.5; 135.5;
133.3; 133.2; 129.7; 129.7; 127.7; 127.7; 127.6; 127.6; 110.0; 102.2 (C(1')); 78.5 (C(3')); 73.8 (C(2')); 73.6 (C(5'));
73.1 (C(4')); 72.0(C(3)); 68.8 (C(1)); 64.8 (C(2)); 62.4 (C(6 ')); 33.3; 31.9; 30.2; 30.2; 29.8; 29.7; 29.7; 29.7; 29.7;
29.6; 29.6; 29.6; 29.4; 28.7; 28.2; 26.7; 26.7; 26.7; 26.3; 25.8; 25.8; 25.8; 22.7; 19.2; 18.0; 15.7; 15.7; 14.1; 10.9; 1.0;
‡
‡
À4.5; À4.6. HR-MS (MALDI-FT): 972.6281 ([M ‡ Na] , C54H91N3NaO7Si2 ; calc. 972.6293).
(2S,3R)-2-Azido-3-[(tert-butyl)dimethylsilyloxy]1-{6-O[(tert-butyl)diphenylsilyl]-3,4-O-isopropylidene-2-
O-(3-methylbut-2-enyl)-b-d-galactopyranosyloxy}-10-[(1R,2S)-2-decylcyclopropyl]decane (57). To a soln. of
56 (46 mg, 48 mmol) in dry DMF (1 ml) at 08 was added NaH (60% in mineral oil, 3 mg, 58 mmol) in one portion.
The mixture was stirred for 5 min followed by the addition of prenyl bromide (11 ml, 97 mmol). The resulting
mixture was then stirred at 08 for 5 h before it was diluted with AcOEt (7 ml) and washed with H2O (2 ml) and
brine (2 ml). The org. layer was dried (MgSO4) and concentrated to give the crude product as a viscous oil,
which was then purified by FC (silica gel; 10% AcOEt in hexanes) to afford 57 (42 mg, 85%). Clear oil. Rf 0.71
(silica gel; 17% AcOEt in hexanes). [a]D ˆ ‡5.5 (c ˆ 2.8, CHCl3). FT-IR (neat): 2928, 2856, 2110, 1462, 1377,
1251, 1106, 833, 702, 608. 1H-NMR (600 MHz, CDCl3): 7.70± 7.66 ( m, 4 arom. H); 7.43 ± 7.34 (m, 6 arom. H);
5.37 (t, J ˆ 7.1, Me2CCHCH2); 4.23 (m, HÀC(4'), Me2CCHCH2); 4.20( d, J ˆ 8.1, HÀC(1')); 4.05 (dd, J ˆ 5.8,
6.9, HÀC(3'); 3.94 (dd, J ˆ 7.5, 9.9, HÀC(6')); 3.90± 3.84 ( m, 1 HÀC(6'), 1 HÀC(1)); 3.79 ± 3.73 (m, HÀC(3),
HÀC(5')); 3.64 (td, J ˆ 4.5, 7.8, HÀC(2)); 3.55 (dd, J ˆ 4.6, 10.3, 1 HÀC(1)); 3.29 (t, J ˆ 7.4, HÀC(2')); 1.72
(s, 3 H); 1.67 (s, 3 H); 1.61 ± 1.55 (m, 1 H); 1.48 (s, 3 H); 1.40± 1.20( m, 32 H); 1.12 ± 1.09 (m, 2 H); 1.0 3 (s, 9 H);
0.87 ± 0.83 (m, 12 H); 0.65 ± 0.63 (m, 2 H); 0.57 ± 0.53 (m, 1 H); 0 .0 2 s(, 6 H); À0.35 (m, 1 H). 13C-NMR
(150MHz, CDCl 3): 137.2; 135.6; 135.6; 135.5; 135.5; 133.4; 133.2; 129.7; 129.7; 127.7; 127.7; 127.6; 127.6; 121.4;
109.6; 102.9 (C(1')); 79.3 (C(2')); 79.1 (C(3')); 73.2 (C(5')); 73.2 (C(4')); 72.3 (C(3')); 68.6 (C(1)); 68.4
(Me2CCHCH2); 65.5 (C(2)); 62.5 (C(6')); 32.5; 31.9; 30.2; 29.9; 29.7 (5 C); 29.4, 28.7; 28.6; 28.0; 27.3; 27.3; 26.7;
26.3; 25.8; 25.8; 25.8; 25.0; 24.5; 22.7; 19.2; 18.0; 18.0; 15.7; 15.7; 14.1; 10.9; À4.5; À4.6. HR-MS (MALDI-FT):
‡
‡
1040.6917 ([M ‡ Na] , C59H99N3NaO7Si2 ; calc. 1040.6919).

Helvetica Chimica Acta ± Vol. 83 (2000)
1999
(2S,3R)-2-Amino-3-[(tert-butyl)dimethylsilyloxy]-1-{6-O-[(tert-Butyl)diphenylsilyl]-3,4-O-isopropylidene-2-
O-(3-methylbut-2-enyl)-b-d-galactopyranosyloxy}-10-[(1R,2S)-2-decylcyclopropyl]decane (58). A soln. of 57
(40mg, 39 mmol) and Ph3P (21 mg, 79 mmol) in benzene (1.0ml) was heated at 45 8 for 1 h before addition of
H2O (2 ml), followed by heating at 458 for 7.5 h. Dilution with AcOEt (5 ml) and washing with sat. aq. NH4Cl
soln. (3 ml) and brine (3 ml) was followed by drying (MgSO4). Concentration in vacuo gave the crude product
as a viscous oil, which was then purified by FC (silica gel; 12% AcOEt in hexanes) to afford pure 58 (35 mg,
90%). Clear oil. Rf 0.17 (silica gel; 17% AcOEt in hexanes). [a]D ˆ ‡2.2 (c ˆ 3.0, CHCl3). FT-IR (neat): 3385,
1
2927, 1464, 1380, 1247, 1082, 1044, 833, 704. H-NMR (600 MHz, CDCl3): 7.70± 7.65 ( m, 4 arom. H); 7.43 ± 7.33
(m, 6 arom. H); 5.36 (t, J ˆ 6.7, Me2CCHCH2); 4.27 ± 4.19 (m, HÀC(4'), Me2CCHCH2); 4.20( d, J ˆ 8.0,
HÀC(1')); 4.05 (t, J ˆ 6.4, 1 HÀC(3')); 3.94 ± 3.85 (m, CH2(6')); 3.77 (t, J ˆ 6.4, HÀC(5')); 3.68 ± 3.64
(m, 1 HÀC(1), HÀC(8)); 3.60( dd, J ˆ 4.1, 9.7, 1 HÀC(1)); 3.28 (t, J ˆ 7.6, HÀC(2')); 3.00 (td, J ˆ 4.1, 8.2,
HÀC(2)); 1.71 (s, 3 H); 1.69 ± 1.54 (m, 5 H); 1.52 ± 1.48 (m, 4 H); 1.45 ± 1.18 (m, 32 H); 1.18 ± 1.05 (m, 2 H); 1.03
(s, 9 H); 0.86 (t, J ˆ 6.8, 3 H); 0.82 (s, 9 H); 0.65 ± 0.60 (m, 2 H); 0.57 ± 0.52 (m, 1 H); 0 .0 1s(, 3 H); 0.00 (s, 3 H);
À0.35 (m, 1 H). 13C-NMR (150MHz, CDCl 3): 137.2; 135.6; 135.6; 135.5; 135.5; 133.4; 133.2; 129.7; 129.7; 127.7;
127.7; 127.6; 127.6; 121.4; 109.6; 102.9 (C(1')); 79.3 (C(2')); 79.1 (C(3')); 73.9 (C(3)); 73.2 (C(4')); 73.0(C(5 '));
71.7 (C(1)); 68.3 (Me2CCHCH2); 62.4 (C(6')); 54.5 (C(2)); 32.7; 31.9; 30.2; 30.2; 29.9; 29.7; 29.7; 29.7; 29.6; 29.6;
29.6; 29.4; 28.7; 28.7; 28.0; 26.7; 26.7; 26.7; 26.3; 25.8; 25.8; 25.8; 25.8; 25.2; 22.7; 19.2; 18.1; 18.0; 15.7; 15.7; 14.1;
‡
‡
10.9; À4.3; À4.6. HR-MS (MALDI-FT): 1014.6968 ([M ‡ Na] , C59H101NNaO7Si2 ; calc. 1014.7014).
(2R,5Z)-N-{(1S,2R)-2-[(tert-Butyl)dimethylsilyloxy]-1-({6-O-[(tert-butyl)diphenylsilyl]-3,4-O-isopropy-
lidene-2-O-(3-methylbut-2-enyl)-b-d-galactopyranosyloxy}methyl)-9-[(1R,2S)-2-decylcyclopropyl]nonyl}-2-hy-
droxydec-5-enamide (59). A mixture of 58 (30mg, 30 mmol) and 12 (17 mg, 45mmol) were azeotroped with
benzene (3 Â 3 ml) and dried further under vacuum for 2 h prior reaction. The mixture was cooled to 08 under
Ar and dry THF (4 ml) was added. HOAt (12 mg, 91 mmol) was added, followed by EDC (17 mg, 88 mmol). The
mixture was stirred at 08 for 5 h, before it was diluted with AcOEt (5 ml) and washed with sat. aq. NaHCO3 soln.
(3 ml), H2O (3 ml) and brine (3 ml). The org. layer was dried (MgSO4) and concentrated in vacuo to give the
crude product, which was purified by FC (silica gel; 17% AcOEt in hexanes) to afford 59 (35 mg, 86%) and its
diastereoisomer (5 mg, 12%) as colorless oils.
Data of 59: Rf 0.47 (silica gel; 30% AcOEt in hexanes). [a]D ˆ ‡9.9 (c ˆ 3.0, CHCl3): FT-IR (neat): 3401,
2926, 2855, 1654, 1521, 1463, 1380, 1248, 1081, 833, 703. 1H-NMR (600 MHz, C5D5N, 300 K): 7.98 (d, J ˆ 9.5,
NH); 7.90± 7.86 ( m, 4 arom. H); 7.74 (br. s, OH); 7.50± 7.44 ( m, 6 arom. H); 5.66 ± 5.60( m, Me2CCHCH2,
HÀC(5)); 5.56 ± 5.50( m, HÀC(6)); 4.74 ± 4.72 (m, HÀC(1')); 4.62 (d, J ˆ 8.0, HÀC(1'')); 4.60± 4.56
(m, Me2CCHCH2, HÀC(2)); 4.48 ± 4.45 (m, HÀC(4''), 1 H of CH2ÀC(1')); 4.36 (t, J ˆ 6.8, HÀC(3'')); 4.26
(dd, J ˆ 7.3, 9.7, 1 HÀC(6'')); 4.22 ± 4.13 (m, HÀC(5''), 1 HÀC(6''), HÀC(2')); 3.92 (dd, J ˆ 4.0, 10.2, 1 H of
CH2ÀC(1')); 3.66 (t, J ˆ 7.6, HÀC(2'')); 2.60± 2.58 ( m, 2 H); 2.33 ± 2.30( m, 1 H); 2.19 ± 2.09 (m, 3 H); 1.80±
1.73 (m, 2 H); 1.70( s, 3 H); 1.68 (s, 3 H); 1.65 ± 1.52 (m, 5 H); 1.50± 1.18 ( m, 53 H); 1.15 (s, 9 H); 0.97 (s, 9 H);
0.87 (t, J ˆ 6.8, 6 H); 0.76 ± 0.64 (m, 6 H); 0.27 (s, 3 H); 0.20 (s, 3 H); À0.19 ± À 0.25 (m, 2 H). 13C-NMR
(150MHz, C 5D5N, 300K): 174.6 (C(1)); 136.0(arom. C); 136.0(arom. C); 136.0(arom. C); 136.0(arom. C);
135.9 (Me2CCHCH2); 133.9 (arom. C); 133.8 (arom. C); 130.9 (C(6)); 130.3 (Me2CCHCH2); 130.3 (arom. C);
129.7 (C(5)); 128.3 (arom. C); 128.3 (arom. C); 128.2 (arom. C); 128.2 (arom. C); 122.9 (C(8')); 109.7
(Me2CO2); 104.0 (C(1'')); 79.8 (C(2'')); 79.7 (C(3'')); 74.0(C(4 '')); 73.7 (C(1')); 73.0(C(5 '')); 71.8 (C(2')); 69.3
(CH2ÀC(1')); 68.4 (Me2CCHCH2); 63.5 (C(6'')); 52.2 (C(2)); 35.9; 34.3; 32.1; 32.1; 30.8; 30.6; 30.6; 30.6; 30.3,
30.2; 30.1; 30.1; 30.1; 30.0 (7 C); 29.9; 29.6; 29.6; 29.1; 29.0; 29.0; 29.0; 28.3; 27.7; 26.9; 26.9; 26.9; 26.6; 26.2; 26.2;
25.8; 25.0; 23.9; 23.0; 22.9; 19.4; 18.4; 18.3; 16.2; 16.2; 16.1; 14.3; 14.3; 11.4; 11.4; À4.0; À4.3. HR-MS (MALDI-
‡
‡
FT): 1362.9943 ([M ‡ Na] , C82H141NNaO9Si2 ; calc. 1363.0042).
(2R,5Z)-10-[(1R,2S)-2-Decylcyclopropyl]-N-((1S,2R)-9-[(1R,2S)-2-decylcyclopropyl]-2-hydroxy-1-{[3,4-
O-isopropylidene-2-O-(3-methylbut-2-enyl)-b-d-galactopyranosyloxy]methyl}nonyl)-2-hydroxydec-5-enamide (60).
To a soln. of 59 (30mg, 22 mmol) in dry THF (1.5 ml) at 08 was added a soln. of TBAF (1.0m in THF, 62 ml).
The mixture was allowed to warm to 258 and then stirred further for 8 h. The mixture was diluted with AcOEt
(5 ml), and washed with sat. aq. NH4Cl soln. (2 ml), H2O (2 ml), and brine (2 ml). The org. layer was dried
(MgSO4) and concentrated in vacuo to give the crude product as a viscous oil, which was then purified by FC
(silica gel; 7% MeOH in CH2Cl2) to afford 60 (21.5 mg, 97%). Colorless oil. Rf 0.56 (silica gel; 7% MeOH in
CH2Cl2). [a]D ˆ ‡11.2 (c ˆ 2.1, CHCl3). FT-IR (neat): 3392, 2925, 2854, 1651, 1529, 1462, 1379, 1231, 1080, 1044,
873. 1H-NMR (600 MHz, C5D5N, 300 K): 8.23 (d, J ˆ 9.1, NH); 5.80(br. s, OH); 5.62 ± 5.57 (m, HÀC(5),
Me2CCHCH2); 5.53 ± 5.49 (m, HÀC(6)); 4.71 ± 4.70( m, 1 H of CH2ÀC(1'), HÀC(1')); 4.63 ± 4.57
(m, HÀC(1''), HÀC(2), 1 H of Me2CCHCH2); 4.54 (dd, J ˆ 6.3, 1 H of Me2CCHCH2); 4.43 (dd, J ˆ 2.0, 5.5,
HÀC(4'')); 4.33 ± 4.30( m, HÀC(3''), HÀC(5'')); 4.24 (dd, J ˆ 5.3, 11.2, HÀC(6'')); 4.16 ± 4.12 (m, 1 HÀC(6''),

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Helvetica Chimica Acta ± Vol. 83 (2000)
HÀC(2')); 4.04 (d, J ˆ 6.5, 1 H of CH2ÀC(1')); 3.69 (t, J ˆ 7.5, HÀC(2'')); 3.00 (br. s, OH); 2.60± 2.56 ( m, 2 H);
2.33 ± 2.30( m, 1 H); 2.20± 2.11 ( m, 3 H); 1.96 ± 1.82 (m, 3 H); 1.75 ± 1.66 (m, 1 H); 1.64 (s, 3 H); 1.63 (s, 3 H);
1.62 ± 1.50( m, 5 H); 1.50± 1.17 ( m, 54 H); 0.85 (t, J ˆ 6.7, 6 H); 0.75 ± 0.60 (m, 6 H); À0.22 ± À 0.26 (m, 2 H).
13C-NMR (150MHz, C 5D5N, 300 K): 174.9; 136.0; 130.9; 129.7; 123.1; 109.7; 104.3; 79.9; 79.6; 75.0; 74.6; 71.9;
71.2; 70.0; 68.3; 61.9; 54.2; 35.8; 34.9; 32.1; 32.1; 30.6; 30.6; 30.6; 30.2; 30.2; 30.1; 30.0 (8 C); 29.9; 29.9; 29.6; 29.6;
29.0; 29.0; 29.0; 28.9; 28.3; 27.7; 26.6; 26.6; 23.8; 22.9; 22.9; 20.4; 18.1; 16.2; 16.2; 16.2; 16.1; 14.3; 14.3; 11.4; 11.4.
‡
‡
HR-MS (MALDI-FT): 1010.8004 ([M ‡ Na] , C60H109NaNO9 ; calc. 1010.8000).
(2R,5Z)-10-[(1R,2S)-2-Decylcyclopropyl]-N-((1S,2R)-9-[(1R,2S)-2-decylcyclopropyl]-2-hydroxy-1-{[2-O-
(3-methylbut-2-enyl)-b-d-galactopyranosyloxy]methyl}nonyl)-2-hydroxydec-5-enamide (Plakoside A; 1). To a
soln. of 60 (20mg, 21 mmol) in MeOH (1.0ml) at 25 8 was added 1.0n aq. HCl soln. (20 ml). The mixture was then
heated at 378 for 5 h. The mixture was allowed to cool and diluted with AcOEt (5 ml). The org. layer was
washed with sat. aq. NaHCO3 soln. (2 ml), H2O (2 ml), H2O (2 ml), and brine (2 ml), dried (MgSO4), and
concentrated in vacuo. The crude product was purified by FC (silica gel; 7% MeOH in CH2Cl2) to afford 1
(18.4 mg, 96%). Amorphous solid. Rf 0.27 (silica gel; 7% MeOH in CH2Cl2). [a]D ˆ ‡10.4 (c ˆ 1.6, MeOH).
1
FT-IR (CHCl3 soln.): 3401, 2925, 2857, 1658, 1528, 1465, 1380, 1082. H-NMR (600 MHz, C5D5N, 300 K): 8.24
(d, J ˆ 9.4, NH); 5.67 (t, J ˆ 6.8, Me2CCHCH2); 5.61 ± 5.57 (m, HÀC(5)); 5.53 ± 5.48 (m, HÀC(6)); 4.79 (dd, J ˆ
4.8, 10.0, 1 H of CH2ÀC(1')); 4.73 ± 4.70( m, HÀC(1'), HÀC(1''), 1 H of Me2CCHCH2); 4.60( dd, J ˆ 3.7, 7.9,
HÀC(2)); 4.56 (dd, J ˆ 7.2, 11.7, 1 H of Me2CCHCH2); 4.46 (d, J ˆ 3.0, HÀC(4'')); 4.41 ± 4.34 (m, CH2(6''));
4.20± 4.18 ( m, HÀC(2')); 4.07 ± 4.01 (m, 1 H of CH2ÀC(1'), HÀC(2''), HÀC(3'')); 3.92 (t, J ˆ 6.0, HÀC(5''));
2.62 ± 2.59 (m, CH2(4)); 2.33 ± 2.28 (m, 1 HÀC(3)); 2.16 ± 2.12 (m, 1 HÀC(3), Me2CCHCH2); 1.98 ± 1.84
(m, CH2(4), 1 HÀC(5')); 1.68 ± 1.56 (m, 1 HÀC(5'), Me2CCHCH2); 1.44 ± 1.15 (m, 56 H); 0.85 (t, J ˆ 6.8,
2 Me); 0.75 ± 0.66 (m, 4 H, HÀC(1) and HÀC(2) of cyclopropyls); 0.66 ± 0.62 (m, 1 H of CH2 of cyclopropyls);
À0.21 ± À 0.25 (m, 1 H of CH2 of cyclopropyls). 13C-NMR (150MHz, C 5D5N, 300 K): 174.9 (C(1)); 134.9
(Me2CCHCH2); 130.8 (C(6)); 129.7 (C(5)); 123.1 (Me2CCHCH2); 105.5 (C(1'')); 79.8 (C(2'')); 77.0(C(5 '')); 74.5
(C(3'')); 71.9 (C(2)); 71.2 (C(2')); 70.3 (C(4'')); 69.9 (CH2ÀC(1')); 69.6 (Me2CCHCH2); 62.2 (C(6'')); 54.4
(C(1')); 35.8 (C(3)); 34.9 (C(3')); 32.1 (2 MeCH2CH2); 30.6 (3 C); 30.3 (3 C); 30.1 ± 29.9 (10 C); 29.6 (2 C); 29.0
(C(9'), C(10), C(10)CHCHCH2, C(9')CHCHCH2); 27.7 (Me2CCHCH2); 26.8 (C(4')); 25.7 (1 Me2CCHCH2);
23.8 (C(4)); 22.9 (2 MeCH2); 18.1 (1 MeCCHC2); 16.2 (4 CH of cyclopropyls); 14.3 (2 Me); 11.4 (2 CH2 of
‡
‡
cyclopropyl). HR-MS (MALDI-FT: 970.7656 ([M ‡ Na] , C57H105NNaO9 ; calc. 970.7687).
(2S,3R,7Z)-2-Azido-3-[(tert-butyl)dimethylsilyloxy]-1-{6-O-[(tert-butyl)diphenylsilyl]-3,4-O-isopropylidene-
2-O-(trimethylacetyl)-b-d-galactopyranosyloxy}-12-[(1R,2S)-2-decylcyclopropyl]dodec-7-ene (61). The proto-
col was followed as for 55 prior to the glycosidation reaction. To a stirred mixture of AgOTf (219 mg, 851 mmol),
SnCl2 (161 mg, 851 mmol), and activated 4-Š molecular sieves (500 mg) in dry CH2Cl2 (5 ml) under Ar at 08, was
added a soln. of 14 (148 mg, 284 mmol) and glycosyl fluoride 11 (309 mg, 567 mmol) in dry CH2Cl2 (5 ml) via
syringe. To this mixture was added 2,6-di(tert-butyl)-4-methylpyridine (70mg, 340 mmol) in one portion. The
mixture was stirred at 08 in the dark for 3 h before it was allowed to warm to 258 and stirred further for 3.5 h. The
mixture was diluted with AcOEt (15 ml) and filtered through a pad of Celite and rinsed with AcOEt (10ml).
The org. filtrate was washed with sat. aq. NaHCO3 soln. (2 Â 5 ml), H2O (7 ml), and brine (7 ml). The org.
extract was dried (MgSO4) and concentrated in vacuo to a crude oil, which was then purified by FC (silica gel;
5% AcOEt in hexanes) to afford 61 (292 mg, 98%). Colorless oil. Rf 0.38 (silica gel; 10% AcOEt in hexanes).
[a]D ˆ ‡3.2 (c ˆ 2.0, CHCl3). FT-IR (neat): 3054, 2928, 2856, 2099, 1740, 1462, 1428, 1379, 1256, 1222, 1112, 830,
778, 704, 504. 1H-NMR (500 MHz, CDCl3): 7.70± 7.66 ( m, 4 arom. H); 7.43 ± 7.34 (m, 6 arom. H); 5.58 ± 5.27
(m, HÀC(7), HÀC(8)); 4.95 (t, J ˆ 7.7, H ÀC(2')); 4.34 (d, J ˆ 8.1, HÀC(1')); 4.29 (dd, J ˆ 1.8, 5.5, HÀC(4'));
4.14 (dd, J ˆ 5.4, 7.3, HÀC(3')); 3.97 (dd, J ˆ 9.5, 12.3, 1HÀC(6')); 3.91 (dd, J ˆ 9.5, 12.3, 1 HÀC(6')); 3.88 ± 3.85
(m, HÀC(5')); 3.78 (dd, J ˆ 8.5, 11.7, 1 HÀC(1)); 3.73 ± 3.70( m, HÀC(3)); 3.54 ± 3.51 (m, 1 HÀC(1), HÀC(2));
2.01 ± 1.97 (dd, J ˆ 6.6, 13.6, CH2(6), CH2(9)); 1.56 ± 1.54 (m, 1 HÀC(4), 1 Me of Me2CCHCH2); 1.42 ± 1.12
(m, 39 H); 1.0 4 (s, t-Bu); 0.87 (t, J ˆ 7.0, MeCH2); 0.84 (s, t-Bu); 0.63 (m, 2 CH of cyclopropyl); 0.57 ± 0.53
(m, 1 H of cyclopropyl); 0.02 (s, Me2Si), À0.34 (m, 1 H of CH2 of cyclopropyl). 13C-NMR (125 MHz, CDCl3):
176.8; 135.6; 135.6; 135.5; 135.5; 133.3; 133.2; 129.7; 129.7; 129.1; 127.7; 127.7; 127.6; 110.3; 100.4; 77.2; 73.4; 73.2;
72.7; 71.9; 67.8; 65.2; 62.4; 38.7; 32.4; 31.9; 30.2; 29.9; 29.7; 29.7; 29.7; 29.7; 29.7; 29.7; 29.4; 28.7; 28.6; 27.7; 27.3;
27.3; 27.1 (4 C); 26.7; 26.7; 26.7; 26.3; 25.8; 25.8; 25.8; 24.8; 22.7; 19.2; 18.0; 15.8; 15.7; 14.1; 10.9; 1.0; À4.6; À4.6.
‡
‡
HR-MS (MALDI-FT): 1082.7000 ([M ‡ Na] , C61H101N3NaO8Si2 ; calc. 1082.7025).
(2S,3R,7Z)-2-Azido-3-[(tert-butyl)dimethylsilyloxy]-1-{6-O-[(tert-butyl)diphenylsilyl]-3,4-O-isopropylidene-
b-d-galactopyranosyloxy}-12-[(1R,2S)-2-decylcyclopropyl]dodec-7-ene (62). To a soln. of 61 (80mg, 75 mmol)
in dry CH2Cl2 (1.5 ml) at À788 was dropwise added a soln. of DIBAL (1.0m in CH2Cl2, 113 ml, 113 mmol). The
mixture was stirred at À788 for 15 min before it was quenched by the addition of MeOH (300 ml). The mixture

Helvetica Chimica Acta ± Vol. 83 (2000)
2001
was diluted with AcOEt (5 ml) and allowed to warm to 258. Sat. aq. soln. of Rochelleꢀs salt (1.5 ml) was added,
and the resulting cloudy mixture was stirred further until it became clear (30min). The org. layer was further
washed with H2O (2 ml), brine (2 ml), dried (MgSO4), and concentrated in vacuo. The crude product was
purified by FC (silica gel; 12% AcOEt in hexanes) to afford pure 62 (73 mg, 99%). Colorless oil. Rf 0.16 (silica
gel; 10% AcOEt in hexanes. [a]D ˆ ‡2.1 (c ˆ 1.3, CHCl3). FT-IR (neat): 3416, 2928, 2856, 2099, 1464, 1379,
1252, 1108, 1032, 832, 778, 704. 1H-NMR (400 MHz, CDCl3): 7.70± 7.66 ( m, 4 arom. H); 7.44 ± 7.32 (m, 6 ar-
om. H); 5.40± 5.27 ( m, HÀC(7), HÀC(8)); 4.29 (dd, J ˆ 1.7, 7.1, HÀC(4')); 4.15 (d, J ˆ 8.2, HÀC(1')); 4.07
(dd, J ˆ 5.5, 7.3, HÀC(3')); 3.97 (dd, J ˆ 9.2, 12.3, HÀC(6)); 3.92 ± 3.83 (m, HÀC(5'), 1 HÀC(6'), 1 HÀC(1));
3.77 ± 3.73 (m, HÀC(3)); 3.66 (dd, J ˆ 7.3, 10.6, HÀC(2')); 3.58 ± 3.53 (m, 1 HÀC(1), HÀC(2)); 2.42 (br. s,
OH); 2.03 ± 1.99 (m, CH2(6), CH2(9)); 1.60± 1.56 ( m, 1 HÀC(4)); 1.42 ± 1.21 (m, 31 H); 1.12 ± 1.09
(m, 1 HÀC(12), 1 H of CH2-cycloproyl); 1.04 (s, t-Bu); 0.87 (t, J ˆ 7.0, MeCH2); 0.84 (s, t-Bu); 0.63 (m, 2 CH
of cyclopropyl); 0.57 ± 0.53 (m, 1 H of CH2 of cyclopropyl); 0.02 (d, J ˆ 2.8, Me2Si); À0.34 (m, 1 H of CH2 of
cyclopropyl). 13C-NMR (100 MHz, CDCl3): 135.6; 135.6; 135.5; 135.5; 133.3; 133.2; 130.6; 129.7; 129.7; 129.0;
127.7; 127.7; 127.5; 127.5; 110.0; 102.2 (C(1')); 78.5 (C(3')); 73.8 (C(5')); 73.6 (C(4')); 73.1 (C(2')); 71.8 (C(3));
67.8 (C(1)); 65.8 (C(2)); 62.4 (C(6')); 32.8; 31.9; 30.2; 29.9; 29.7 (4 C); 29.4; 28.7; 28.6; 28.2; 27.3; 27.2; 26.7; 26.7;
26.7; 26.3; 25.9; 25.9; 25.9; 24.6; 22.7; 19.2; 18.0; 15.7; 15.7; 14.1; 10.9; 1.0; À4.5, À4.6. HR-MS (MALDI-FT):
‡
‡
998.6411 ([M ‡ Na] , C56H93N3NaO7Si2 ; calc. 998.6449).
(2S,3R,7Z)-2-Azido-3-[(tert-butyl)dimethylsilyoxy]-1-{6-O-[(tert-butyl)diphenylsilyl]-3,4-O-isopropylidene-
2-O-(3-methylbut-2-enyl)-b-d-galactopyranosyloxy}-12-[(1R,2S)-2-decylcyclopropyl]dec-7-ene (63). To a soln.
of 62 (70mg, 72 mmol) in dry DMF (1 ml) at 08 was added NaH (60% in mineral oil, 3.7 mg, 84 mmol) in one
portion. The mixture was stirred for 5 min followed by the addition of prenyl bromide (12 ml, 108 mmol). The
mixture was then stirred at 08 for 5 h before it was diluted with AcOEt (7 ml) and washed with H2O (2 ml) and
brine (2 ml). The org. layer was dried (MgSO4) and concentrated in vacuo to give the crude product as a viscous
oil, which was then purified by FC (silica gel; 12% AcOEt in hexanes) to afford 63 (64 mg, 85%). Colorless oil.
Rf 0.16 (silica gel; 17% AcOEt in hexanes). [a]D ˆ ‡5.7 (c ˆ 3.5, CHCl3). FT-IR (neat): 2928, 2855, 2099, 1463,
1378, 1254, 1110, 1044, 833, 704. 1H-NMR (500 MHz, CDCl3): 7.70± 7.66 ( m, 4 arom. H); 7.43 ± 7.34
(m, 6 arom. H); 5.39 ± 5.28 (m, HÀC(7), HÀC(8), Me2CCHCH2); 4.25 ± 4.24 (m, HÀC(4'), Me2CCHCH2);
4.20( d, J ˆ 8.1, HÀC(1')); 4.06 (t, J ˆ 6.9, HÀC(3')); 3.94 (dd, J ˆ 7.7, 9.8, 1 HÀC(6')); 3.90± 3.84
(m, 1 HÀC(1), 1 HÀC(6')); 3.79 ± 3.73 (m, HÀC(3), HÀC(5')); 3.66 ± 3.62 (m, HÀC(2)); 3.55 (dd, J ˆ 4.6,
10.3, 1 HÀC(1)); 3.30( t, J ˆ 7.4, HÀC(2')); 2.00 ± 1.96 (m, CH2(6), CH2(9)); 1.72 (s, 1 Me2CCHCH2); 1.67
(s, 1 Me2CCHCH2); 1.61 ± 1.55 (m, 1 HÀC(4)); 1.48 ± 1.25 (m, 31 H); 1.12 ± 1.09 (m, HÀC(12), 1 H of CH2-
cyclopropyl); 1.04 (s, t-Bu); 0.87 (t, J ˆ 7.0, MeCH2); 0.85 (s, t-Bu)); 0.63 (m, 2 CH of cyclopropyl); 0.57 ± 0.54
(m, 1 H of CH2 of cyclopropyl); 0.03 (s, Me2Si); À0.34 (m, 1 H of CH2 cyclopropyl). 13C-NMR (100 MHz,
CDCl3): 137.2; 135.6; 135.6; 135.5; 135.5; 133.3; 133.2; 130.5; 129.7; 129.7; 129.1; 127.7; 127.7; 127.7; 127.6; 121.4;
110.0; 109.7; 102.6 (C(1')); 79.3 (C(2')); 79.1 (C(3')); 73.2 (C(5')); 73.2 (C(4')); 72.3 (C(3)); 68.6 (C(1)); 68.4
(Me2CCHCH2); 65.5 (C(2)); 62.5 (C(6')); 32.5; 31.9; 30.2; 29.9; 29.7 (4 C); 29.4; 28.7; 28.6; 28.0; 27.3; 27.3; 26.7;
26.7; 26.7; 26.3; 25.8; 25.8; 25.8; 25.0; 24.6; 22.7; 19.2; 18.1; 18.0; 15.7; 15.7; 14.1; 10.9; À4.5; À4.6. HR-MS
‡
‡
(MALDI-FT): 1066.7048 ([M ‡ Na] , C61H101N3NaO7Si2 ; calc. 1066.7075).
(2S,3R,7Z)-2-Amino-3-[(tert-butyl)dimethylsilyloxy]-1-{6-O-[(tert-butyl)diphenylsilyl]-3,4-O-isopropylidene-
2-O-(3-methylbut-2-enyl)-b-d-galactopyranosyloxy}-12-[(1R,2S)-2-decylcyclopropyl]dec-7-ene (64). A soln. of
63 (56 mg, 54 mmol) and Ph3P (28 mg, 107 mmol) in benzene (1 ml) was heated at 458 for 1 h before H2O (2 ml)
was added. The mixture was then heated at 458 for 7.5 h before it was cooled and diluted with AcOEt (5 ml), and
washed with sat. aq. NH4Cl soln. (3 ml) and brine (3 ml). The org. layer was dried (MgSO4) and concentrated in
vacuo to give the crude product as a viscous oil, which was then purified by FC (silica gel; 12% AcOEt in
hexanes) to afford 64 (47 mg, 86%). Colorless oil. Rf 0.15 (silica gel; 12% AcOEt in hexanes). [a]D ˆ ‡1.8 (c ˆ
3.0, CHCl3). FT-IR (neat): 3389, 2927, 2856, 1461, 1376, 1248, 1083, 1038, 931, 704. 1H-NMR (500 MHz, CDCl3):
7.70± 7.65 ( m, 4 arom. H); 7.43 ± 7.33 (m, 6 arom. H); 5.36 ± 5.30( m, HÀC(7), HÀC(8), Me2CCHCH2); 4.27 ±
4.24 (m, HÀC(4'), Me2CCHCH2); 4.20( d, J ˆ 8.1, HÀC(1')); 4.06 (dd, J ˆ 5.6, 7.0, HÀC(3')); 3.93 (dd, J ˆ 7.7,
9.8, 1 HÀC(6')); 3.87 (dd, J ˆ 9.7, 15.6, 1 HÀC(6')); 3.78 (m, HÀC(5')); 3.68 ± 3.64 (m, 1 HÀC(1), HÀC(3));
3.60( dd, J ˆ 4.2, 5.5, 1 HÀC(1)); 3.29 (t, J ˆ 7.4, HÀC(2')); 3.00 (m, HÀC(2)); 2.02 ± 1.95 (m, CH2(6), CH2(9));
1.71 (s, 1 Me2CCHCH2); 1.65 (s, 1 Me2CCHCH2); 1.61 ± 1.55 (m, 1 HÀC(4)); 1.48 ± 1.25 (m, 33 H); 1.12 ± 1.09
(m, HÀC(12), 1 H of CH2-cyclopropyl); 1.03 (s, t-Bu); 0.87 (t, J ˆ 7.0, MeCH2); 0.85 (s, t-Bu); 0.63 (m, 2 CH of
cyclopropyl); 0.57 ± 0.53 (m, 1 H of CH2 of cyclopropyl); 0.03 (dd, J ˆ 3.6, Me2Si); À0.35 (m, 1 H of CH2 of
cyclopropyl). 13C-NMR (125 MHz, CDCl3): 137.2; 135.6; 135.6; 135.5; 135.5; 133.4; 133.2; 130.3; 129.7; 129.6;
129.3; 127.7; 127.7; 127.6; 127.6; 121.4; 109.6; 109.7; 102.9 (C(1')); 79.3 (C(2')); 79.1 (C(3')); 73.8 (C(3)); 73.2
(C(4')); 73.0(C(5 ')); 71.7 (C(1)); 68.3 (Me2CCHCH2); 62.4 (C(6')); 54.5 (C(2)); 32.3; 31.9; 30.2; 29.9; 29.7 (4 C);

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Helvetica Chimica Acta ± Vol. 83 (2000)
29.3; 28.7; 28.6; 28.0; 27.3; 27.3; 26.7; 26.7; 26.7; 26.3; 25.8; 25.8; 25.8; 25.8; 25.2; 22.7; 19.2; 18.1; 18.0; 15.7; 15.7;
‡
‡
14.1; 10.9; À4.3; À4.6. HR-MS (MALDI-FT): 1040.7172 ([M ‡ Na] , C61H103NNaO7Si2 ; calc. 1040.7170).
(2R,5Z)-N-[(1S,2R,6Z)-2-[(tert-Butyl)dimethylsilyloxy]-1-({6-O-[(tert-butyl)diphenylsilyl]-3,4-O-isopro-
pylidene-2-O-(3-methylbut-2-enyl)-b-d-galactopyranosyloxy}methyl)-11-[(1R,2S)-2-decylcyclopropyl]undec-6-
enyl]-10-[(1R,2S)-2-decylcyclopropyl]-2-hydroxydec-5-enamide (65). A mixture of 64 (42 mg, 41 mmol) and 12
(23 mg, 62 mmol) were azeotroped with benzene (3 Â 3 ml) and dried further under vacuum for 2 h. The mixture
was cooled to 08 under Ar, and dry THF (4 ml) was added. HOAt (17 mg, 128 mmol) was added, followed by
EDC (24 mg, 124 mmol). The mixture was stirred at 08 for 5 h, and then diluted with AcOEt (5 ml) and washed
with sat. aq. NaHCO3 soln. (3 ml), H2O (3 ml), and brine (3 ml). The org. layer was dried (MgSO4) and
concentrated in vacuo to give the crude product as a viscous oil, which was then purified by FC (silica gel; 7%
AcOEt in hexanes) to afford 65 (48 mg, 86%). Colorless oil. Rf 0.47 (silica gel; 30% AcOEt in hexanes). [a]D
ˆ
‡9.4 (c ˆ 2.5, CHCl3). FT-IR (neat): 3401, 2926, 2855, 1654, 1520, 1463, 1379, 1248, 1155, 1083, 1038, 833, 703,
507. 1H-NMR (600 MHz, C5D5N, 300 K): 7.98 (d, J ˆ 9.4, NH); 7.90± 7.86 ( m, 4 arom. H); 7.50± 7.44 ( m, 6 ar-
om. H); 5.64 ± 5.60( m, HÀC(5), Me2CCHCH2); 5.56 ± 5.53 (m, HÀC(6), HÀC(6'), HÀC(7')); 4.74 ± 4.72
(m, HÀC(1')); 4.62 ± 4.56 (m, HÀC(2), HÀC(1''), Me2CCHCH2); 4.48 ± 4.45 (m, HÀC(4''), 1 H of
CH2ÀC(1')); 4.36 (t, J ˆ 6.8, HÀC(3'')); 4.26 (t, J ˆ 9.4, 1 HÀC(6'')); 4.22 ± 4.13 (m, HÀC(2'), HÀC(5''),
1 HÀC(6'')); 3.90( dd, J ˆ 3.7, 10.2, 1 H of CH2ÀC(1')); 3.65 (t, J ˆ 7.8, HÀC(2'')); 2.59 (m, CH2(4)); 2.33 ± 2.31
(m, 1 HÀC(3)); 2.19 ± 2.09 (m, 1 HÀC(3), CH2(5'), CH2(8')); 1.85 ± 1.75 (m, 3 H); 1.75 ± 1.71 (s, Me); 1.69
(s, Me); 1.57 ± 1.18 (m, 58 H); 1.15 (s, t-Bu); 0.98 (s, t-Bu)); 0.87 (t, J ˆ 7.0, 2 MeCH2); 0.74 ± 0.64 (m, 4 CH of
cyclopropyls, 1 H of CH2 of cyclopropyls); 0.24 (dd, J ˆ 40.1, Me2Si); À0.18 ± À 0.24 (m, 1 H of CH2
cyclopropyls). 13C-NMR (150MHz, C 5D5N, 300 K): 174.6 (C(1)); 136.0 (arom. C); 136.0 (arom. C); 136.0
(arom. C); 136.0(arom. C); 135.8 (Me 2CCHCH2); 133.9 (arom. C); 133.8 (arom. C); 130.9 (C(6)); 130.6
(C(7')); 130.3 (arom. C); 130.3 (arom. C); 130.0 (Me2CCHCH2); 129.7 (C(5)); 128.3 (arom. C); 128.3
(arom. C); 128.2 (arom. C); 128.2 (arom. C); 123.1 (Me2CCHCH2); 109.7 (Me2CO2); 104.0 (C(1'')); 79.8
(C(2'')); 79.7 (C(3'')); 74.0(C(4 '')); 73.7 (C(5'')); 72.8 (C(2')); 71.8 (C(2)); 69.3 (CH2ÀC(1')); 68.4
(Me2CCHCH2); 63.5 (C(6'')); 52.2 (C(1')); 35.9, 33.8; 32.2; 32.2; 30.8; 30.6; 30.3; 30.3; 30.2; 30.1; 29.9 (10 C);
29.7; 29.7; 29.1; 29.0; 29.0; 28.9; 28.3; 27.8; 27.7; 27.0; 27.0; 27.0; 26.6; 26.2; 26.2; 26.2; 25.8; 25.0; 24.0; 23.0; 23.0;
19.4; 18.4; 18.3; 16.2; 16.2; 16.2; 14.3; 14.3; 11.4; 11.4; À4.0; À4.3. HR-MS (MALDI-FT): 1389.0269 ([M ‡
‡
‡
Na] , C84H143NNaO9Si2 ; calc. 1389.0199).
(2R,5Z)-10-[(1R,2S)-2-Decylcyclopropyl]-N-((1S,2R,6Z)-11-[(1R,2S)-2-decylcyclopropyl]-2-hydroxy-1-{[3,4-
isopropylidene-2-O-(3-methylbut-2-enyl)-b-d-galactopyranosyloxy]methyl}undec-6-enyl)-2-hydroxydec-5-en-
amide (66). To a soln. of 65 (25 mg, 11 mmol) in dry THF (0.5 ml) at 08 was added a soln. of TBAF (1.0m in THF,
55 ml, 55 mmol). The mixture was allowed to warm to 258 and then stirred further for 5 h before it was diluted
with AcOEt (5 ml) and washed with sat. aq. NH4Cl soln. (2 ml), H2O (2 ml), and brine (2 ml). The org. layer
was dried (MgSO4) and concentrated in vacuo to give the crude product as a viscous oil, which was then purified
by FC (silica gel; 7% MeOH in CH2Cl2) to afford 66 (18 mg, 97%). Colorless oil. Rf 0.45 (silica gel; 7% MeOH
in CH2Cl2). [a]D ˆ ‡13.0( c ˆ 2.7, CHCl3). FT-IR (neat): 3389, 2924, 2854, 1652, 1519, 1458, 1378, 1079.
1H-NMR (600 MHz, C5D5N, 300 K): 8.21 (d, J ˆ 9.2, NH); 7.70(br. s, OH); 6.65 (br. s, OH); 6.43 (br. s, OH);
5.61 ± 5.58 (m, HÀC(5), Me2CCHCH2); 5.52 ± 5.46 (m, HÀC(6), HÀC(6'), HÀC(7')); 4.71 ± 4.69 (m, HÀC(1'),
1 H of CH2ÀC(1')); 4.60± 4.57 ( m, HÀC(2), HÀC(1''), 1 H of Me2CCHCH2); 4.54 ± 4.51 (m, 1 H of
Me2CCHCH2); 4.43 (dd, J ˆ 2.0, 5.5, HÀC(4'')); 4.33 ± 4.30( m, HÀC(3''), HÀC(5'')); 4.24 (dd, J ˆ 5.3, 11.2,
1 HÀC(6'')); 4.16 ± 4.14 (m, HÀC(2'), 1 HÀC(6'')); 4.03 ± 4.02 (m, 1 H of CH2ÀC(1')); 3.68 (t, J ˆ 12.0,
HÀC(2'')); 2.60± 2.59 ( m, CH2(4)); 2.31 ± 2.30( m, 1HÀC(3)); 2.20± 2.10 ( m, 1 HÀC(3), CH2(7), CH2(5'),
CH2(8')); 1.96 ± 1.84 (m, CH2(3'), 1 HÀC(4')); 1.67 (m, 1 HÀC(4'), Me2C); 1.56 (s, Me); 1.44 ± 1.17 (m, 51 H);
0.85 (t, J ˆ 7.0, 2 MeCH2); 0.71 (m, 4 CH of cyclopropyls); 0.67 ± 0.62 (m, 1 H of CH2 of cyclopropyls); À0.21 ±
À 0.25 (m, 1 H of CH2 of cyclopropyls). 13C-NMR (150MHz, C 5D5N, 300 K): 174.9 (C(1)); 136.0
(Me2CCHCH2); 130.9 (C(6)); 130.3 (C(7')); 130.2 (C(6')); 129.7 (C(5)); 123.1 (Me2CCHCH2); 109.7
(Me2CO2); 104.3 (C(1'')); 79.9; 79.6; 75.0; 74.6; 71.9; 71.1; 69.9; 68.3; 65.8; 61.9; 54.1; 35.8; 34.5; 32.1; 32.1;
30.6; 30.3; 30.2; 30.1; 30.1; 30.0; 29.9 (8 C); 29.6; 29.6; 29.0; 29.0; 29.0; 28.9; 28.3, 27.8; 27.7; 26.8; 26.6; 25.7; 23.9;
‡
22.9; 18.2; 16.2; 16.2; 16.2; 16.1; 14.3; 14.3; 11.4; 11.4. HR-MS (MALDI-FT): 1036.8195 ([M ‡ Na] ,
‡
C62H111NNaO9 ; calc. 1036.8156).
(2R,5Z)-10-[(1R,2S)-2-Decylcyclopropyl]-N-((1S,2R,6Z)-11-[(1R,2S)-2-decylcyclopropyl]-2-hydroxy-1-{[2-
O-(3-methylbut-2-enyl)-b-d-galactopyranosyloxy]methyl}undec-6-enyl)-2-hydroxydec-5-enamide (Plakoside B,
2). To a soln. of 66 (17 mg, 18 mmol) in MeOH (1 ml) at 258 was added aq. HCl soln. (1.0n, 20 ml), and the
mixture was heated at 378 for 5 h. The mixture was cooled and diluted with AcOEt (5 ml), and washed with sat.
aq. NaHCO3 soln. (2 ml), H2O (2 ml), and brine (2 ml). The org. layer was dried (MgSO4) and concentrated in

Helvetica Chimica Acta ± Vol. 83 (2000)
2003
vacuo to give the crude product as a viscous oil, which was then purified by FC (silica gel; 7% MeOH in CH2Cl2)
to afford 2 (16 mg, 98%). Amorphous solid. Rf 0.43 (silica gel; 7% MeOH in CH2Cl2). [a]D ˆ ‡9.6 (c ˆ 1.4,
MeOH). FT-IR (CHCl3 soln.): 3382, 2922, 2852, 1644, 1520, 1454, 1373, 1079. 1H-NMR (600 MHz, C5D5N,
300 K): 8.23 (d, J ˆ 9.3, NH); 5.67 (m, Me2CCHCH2); 5.59 (m, HÀC(5)); 5.53 ± 5.46 (m, HÀC(6), HÀC(6'),
HÀC(7')); 4.79 (dd, J ˆ 4.8, 10.0, 1 H of CH2ÀC(1')); 4.73 ± 4.70( m, HÀC(1'), HÀC(1''), 1 H of Me2CCHCH2);
4.60± 4.55 ( m, HÀC(2), 1 H of Me2CCHCH2); 4.46 (d, J ˆ 2.4, HÀC(4'')); 4.41 ± 4.34 (m, CH2(6'')); 4.19 (t, J ˆ
7.1, H ÀC(2')); 4.07 ± 4.01 (m, HÀC(2''), HÀC(3''), 1 H of CH2ÀC(1')); 3.92 (t, J ˆ 5.8, HÀC(5'')); 2.60± 2.59
(m, CH2(4)); 2.33 ± 2.31 (m, 1 HÀC(3)); 2.21 ± 2.11 (m, 1 HÀC(3), CH2(7), CH2(5'), CH2(8')); 1.98 ± 1.87
(m, CH2(3'), 1 HÀC(4')); 1.67 (m, 1 HÀC(4')); 1.58 (s, Me2CCHCH2); 1.44 ± 1.23 (m, 55 H); 0.85 (t, J ˆ 7.0,
2 MeCH2); 0.71 (m, 4 CH of cyclopropyls); 0.67 ± 0.62 (m, 2 H, 1 H of CH2 of cyclopropyls); À0.21 ± À 0.25
(m, 1 H of CH2 of cyclopropyls). 13C-NMR (150MHz, C 5D5N, 300 K): 174.9 (C(1')); 135.0(Me 2CCHCH2);
130.9 (C(6)); 130.3 (C(7')); 130.2 (C(6')); 129.7 (C(5)); 123.1 (Me2CCHCH2); 105.5 (C(1'')); 79.8 (C(2'')); 77.0
(C(5'')); 74.5 (C(3'')); 71.9 (C(2)); 71.1 (C(2')); 70.3 (C(4'')); 69.9 (CH2ÀC(1')); 69.6 (Me2CCHCH2); 62.2
(C(6'')); 54.3 (C(1')); 35.9 (C(3)); 34.5 (C(3')); 32.1 (2 MeCH2CH2); 30.6; 30.6; 30.3; 30.2; 30.1; 30.1; 30.0; 29.9
(7 C); 29.6; 29.6; 29.0(C(10), C(13), C(11 '), CH2 of cyclopropyl); 27.8 (C(7), C(5'), C(8')); 26.8 (C(4')); 25.7
(1 Me2CCHCH2); 23.9 (C(4)); 22.9 (2 MeCH2CH2); 18.1 (1 Me2CCHCH2); 16.2 (4 CH of cyclopropyls): 14.3
‡
‡
(2 MeCH2); 11.4 (2 CH2 of cyclopropyl). HR-MS (MALDI-FT): 996.7850([ M ‡ Na] , C59H107NNaO9 ; calc.
996.7843).
(2R,5Z)-10-[(1R,2S)-2-Decylcyclopropyl]-N-((1S,2R)-9-[(1R,2S)-2-decylcyclopropyl]-2-hydroxy-1-{[2-O-
(prop-2-enyl)-b-d-galactopyranosyloxy]methyl}nonyl)-2-hydroxydec-5-enamide (3). Amorphous solid. Rf 0.39
(silica gel; 7% MeOH in CH2Cl2).1H-NMR (600 MHz, C5D5N, 300 K): 8.24 (d, J ˆ 10.8, NH); 6.25 ± 6.17
(m, 1 H); 5.63 ± 5.59 (m, 1 H); 5.51 ± 5.42 (m, 2 H); 5.51 (d, J ˆ 12.4, 1 H); 4.76 ± 4.71 (m, 4 H); 4.66 ± 4.64
(m, 1 H); 4.57 ± 4.50( m, 2 H); 4.26 ± 4.21 (m, 2 H); 4.11 ± 4.03 (m, 3 H); 3.92 (t, J ˆ 7.9, 1 H); 2.63 ± 2.59
(m, 2 H); 2.33 ± 2.28 (m, 1 H); 2.16 ± 2.12 (m, 3 H); 1.98 ± 1.84 (m, 3 H); 1.68 ± 1.56 (m, 7 H); 1.44 ± 1.15
(m, 52 H); 0.85 (t, J ˆ 6.9, 6 H); 0.75 ± 0.66 (m, 4 H); 0.66 ± 0.62 (m, 2 H); À0.21 ± À 0.26 (m,2 H). HR-MS
‡
‡
(MALDI-FT): 942.7372 ([M ‡ Na] , C55H101NNaO9 ; calc. 942.7374).
(2R,5Z)-10-[(1R,2S)-2-Decylcyclopropyl]-N-{(1S,2R)-9-[(1R,2S)-2-decylcyclopropyl]-1-({2-O-[(2E,6E)-3,7-
dimethylocta-2,6-dienyl]-b-d-galactopyranosyloxy}methyl)-2-hydroxynonyl}-2-hydroxydec-5-enamide
(4).
Amorphous solid. Rf 0.43 (silica gel; 7% MeOH in CH2Cl2). 1H-NMR (500 MHz, CDCl3): 293 K): 7.48
(d, J ˆ 7.4, NH); 5.43 ± 5.38 (m, 3 H); 5.11 (t, J ˆ 6.2, 1 H); 4.41 ± 4.37 (dd, J ˆ 7, 11.8, 1 H); 4.33 ± 4.23 (m, 4 H);
4.16 ± 4.12 (m, 2 H); 4.08 ± 3.92 (m, 4 H); 3.89 (br. s, 2 H); 3.69 (br. s, 1 H); 3.56 ± 3.55 (m, 1 H); 3.50± 3.48
(m, 2 H); 3.40( t, J ˆ 8.1, 1 H); 3.01 (br. s, 1 H); 2.23 ± 2.22 (m, 2 H); 2.11 ± 2.03 (m, 6 H); 1.98 ± 1.94 (m, 1 H);
1.85 ± 1.82 (m, 6 H); 1.75 ± 1.65 (m, 6 H); 1.62 (s, 3 H); 1.44 ± 1.15 (m,51 H); 0.85 (t, J ˆ 6.6, 6 H); 0.65 ± 0.60
‡
(m, 4 H); 0.55 ± 0.53 (m, 2 H); À0.25 ± À 0.27 (m, 2 H). HR-MS (MALDI-FT): 1038.8317 ([M ‡ Na] ,
‡
C62H113NaNO9 ; calc. 1038.8313).
(2R,5Z)-N-{(1S,2R)-1-[(2-O-Benzyl)-b-d-galactopyranosyloxy)methyl]-9-[(1R,2S)-2-decylcyclopropyl]2-
hydroxynonyl}-10-[(1R,2S)-2-decylcyclopropyl]-2-hydroxydec-5-enamide (5). Amorphous solid. Rf 0.40 (silica
gel; 7% MeOH in CH2Cl2). 1H-NMR (600 MHz, C5D5N, 300 K): 8.30 (d, J ˆ 10.5, NH); 7.68 (d, J ˆ 9.16, 2 H);
7.28 (t, J ˆ 8.8, 2 H); 7.22 (t, J ˆ 7.2, 1 H); 5.57 ± 5.55 (m, 1 H); 5.52 ± 5.47 (m, 1 H); 5.37 (d, J ˆ 14.8, 1 H); 4.99
(d, J ˆ 14.2, 1 H); 4.82 (d, J ˆ 9.2, 1 H); 4.77 ± 4.72 (m, 2 H); 4.61 ± 4.60( m, 1 H); 4.49 ± 4.48 (m, 1 H); 4.44 ± 4.36
(m, 2 H); 4.20± 4.10 ( m, 3 H); 3.95 (t, J ˆ 5.8, 1 H); 2.60± 2.58 ( m, 2 H); 2.32 ± 2.29 (m, 1 H); 2.16 ± 2.12
(m, 3 H); 1.94 ± 1.84 (m, 3 H); 1.68 ± 1.56 (m, 7 H); 1.44 ± 1.15 (m, 52 H); 0.85 (t, J ˆ 6.9, 6 H); 0.75 ± 0.66
‡
(m, 4 H); 0.66 ± 0.62 (m, 2 H); À0.21 ± À 0.26 (m, 2 H). HR-MS (MALDI-FT): 992.77 ([M ‡ Na] ,
‡
C59H103NaNO9 ; calc. 992.7530).
(2R,5Z)-10-[(1R,2S)-2-Decylcyclopropyl]-N-{(1S,2R)-9-[(1R,2S)-2-decylcyclopropyl]-1-[(b-d-galacto-
pyranosyloxy)methyl]-2-[(prop-2-enyl)oxy]nonyl}-2-hydroxydec-5-enamide (6). Amorphous solid. Rf 0.39
(silica gel; 7% MeOH in CH2Cl2). 1H-NMR (500 MHz, CDCl3, 293 K): 7.32 (d, J ˆ 9.2, NH); 5.37 ± 5.28
(m, 3 H); 4.90(br. s, 1 H); 4.76 (br. s, 1 H); 4.39 (br. s, 2 H); 4.23 (d, J ˆ 6.6, 1 H); 4.17 ± 4.10( m, 2 H); 4.02 ±
3.89 (m, 5 H); 3.84 ± 3.82 (m, 3 H); 3.58 (m, 2 H); 3.48 (t, J ˆ 6.2, 1 H); 3.40± 3.39 ( m, 1 H); 2.96 (t, J ˆ 8.1, 1 H);
2.16 (m, 2 H); 2.03 ± 1.94 (m, 5 H); 1.77 ± 1.72 (m, 5 H); 1.64 ± 1.61 (m, 5 H); 1.47 ± 1.11 (m, 49 H); 1.11 ± 1.01
(m, 4 H); 0.86 (t, J ˆ 7.0, 3 H); 0.63 ± 0.61 (m, 4 H); 0.56 ± 0.52 (m, 2 H); À0.26 ± À 0.29 (m, 2 H). HR-MS
‡
‡
(MALDI-FT): 970.7658 ([M ‡ Na] , C57H105NaNO9 ; calc. 970.7687).
(2R,5Z)-10-[(1R,2S)-2-Decylcyclopropyl]-N-((1S,2R,6Z)-11-[(1R,2S)-2-decylcyclopropyl]-2-hydroxy-1-{[2-
O-(prop-2-enyl)-b-d-galactopyranosyloxy]methyl}undec-6-enyl)-2-hydroxydec-5-enamide (7). Amorphous sol-
id. Rf 0.43 (silica gel; 7% MeOH in CH2Cl2). 1H-NMR (600 MHz, C5D5N, 300 K): 8.25 (d, J ˆ 9.2, NH); 6.19 ±
6.12 (m, 1 H); 5.62 ± 5.58 (m, 1 H); 5.52 ± 5.45 (m, 3 H); 5.32 (dd, J ˆ 1.7, 11.7, 1 H); 4.98 (d, J ˆ 10.7, 1 H);

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Helvetica Chimica Acta ± Vol. 83 (2000)
4.73 ± 4.71 (d, 4 H); 4.61 ± 4.59 (m, 1 H); 4.51 ± 4.48 (m, 1 H); 4.46 ± 4.45 (m, 1 H); 4.40± 4.33 ( m, 2 H); 4.16
(t, J ˆ 6.8, 1 H); 4.09 ± 4.02 (m, 3 H); 3.92 (t, J ˆ 5.6, 1 H); 2.60± 2.56 ( m, 2 H); 2.33 ± 2.30( m, 1 H); 2.20± 2.10
(m, 7 H); 1.96 ± 1.92 (m, 3 H); 1.64 ± 1.58 (m, 1 H); 1.45 ± 1.15 (m, 53 H); 0.85 (t, J ˆ 7.0, 6 H); 0.71 (m, 4 H);
0.67 ± 0.62 (m, 2 H); À0.21 ± À 0.26 (m, 2 H). 13C-NMR (150MHz, C 5D5N, 300 K): 174.9; 136.8; 130.8; 130.3;
130.2; 129.7; 116.2; 105.4; 80.3; 77.0; 74.3; 73.9; 71.9; 71.1; 70.3; 69.8; 62.2; 54.2; 35.9; 34.5; 32.1; 32.1; 30.6; 30.6;
30.2; 30.2; 30.1; 30.0 (8 C); 29.9; 29.6; 29.6; 29.0; 29.0; 28.9; 28.9; 27.8; 27.7; 27.7; 26.7; 23.9; 22.9; 22.9; 16.2; 16.2;
‡
‡
16.2; 16.1; 14.3; 14.3; 11.4; 11.4. HR-MS (MALDI-FT): 968.7561 ([M ‡ Na] , C57H103NaNO9 ; calc. 968.7530).
(2R,5Z)-10-[(1R,2S)-2-Decylcyclopropyl]-N-[(1S,2R,6Z)-11-[(1R,2S)-2-decylcyclopropyl]-1-({2-O-[(2E,6E)-
3,7-dimethylocta-2,6-dienyl]-b-d-galactopyranosyloxy}methyl)-2-hydroxydec-5-enamide (8). Amorphous solid.
Rf 0.44 (silica gel; 7% MeOH in CH2Cl2). 1H-NMR (600 MHz, C5D5N, 300 K): 8.25 (d, J ˆ 9.3, NH); 5.73 (t, J ˆ
6.2, 1 H); 5.62 ± 5.59 (m, 1 H); 5.52 ± 5.46 (m, 3 H); 5.14 (t, J ˆ 6.8, 1 H); 4.78 ± 4.72 (m, 4 H); 4.62 ± 4.59
(m, 1 H); 4.46 (d, J ˆ 2.8, 1 H); 4.40± 4.33 ( m, 2 H); 4.20( t, J ˆ 6.8, 1 H); 4.09 ± 4.01 (m, 3 H); 3.92 (t, J ˆ 5.6,
1 H); 2.60± 2.58 ( m, 2 H); 2.33 ± 2.31 (m, 1 H); 2.20± 1.80 ( m, 15 H); 1.70± 1.64 ( m, 7 H); 1.54 (s, 3 H); 1.45 ±
1.15 (m, 53 H); 0.85 (t, J ˆ 7.0, 6 H); 0.71 (m, 4 H); 0.67 ± 0.62 (m, 2 H); À0.21 ± À 0.25 (m, 2 H). 13C-NMR
(150MHz, C 5D5N, 300 K): 174.9; 138.6; 131.3; 130.8; 130.3; 130.2, 129.7; 124.8; 122.6; 105.6; 79.9; 77.0; 74.4;
71.9; 71.2; 70.3; 69.9; 69.7; 62.2; 54.3; 39.9; 35.9; 34.5; 32.1; 32.1; 30.6; 30.6; 30.3; 30.2; 30.2; 30.1; 30.0 (8 C); 29.9;
29.6; 29.6; 29.0; 29.0; 29.0; 28.9; 28.9; 27.8; 27.7; 27.7; 26.9; 26.8; 25.7; 23.9; 22.9; 22.9; 17.7; 16.7; 16.2; 16.2; 16.2;
‡
‡
16.1; 14.3; 14.3; 11.4; 11.4. HR-MS (MALDI-FT): 1064.8511 ([M ‡ Na] , C64H115NNaO9 ; calc. 1064.8469).
(2R,5Z)-N-{(1S,2R,6Z)-1-[(2-O-benzyl-b-d-galactopyranosyloxy)methyl]-11-[(1R,2S)-2-decylcycloprop-
yl]-2-hydroxyundec-6-enyl}-10-[(1R,2S)-2-decylcyclopropyl]-2-hydroxydec-5-enamide (9). Amorphous solid.
Rf 0.44 (silica gel; 7% MeOH in CH2Cl2). 1H-NMR (600 MHz, C5D5N, 300 K): 8.25 (d, J ˆ 9.0, NH); 7.72 (d, J ˆ
7.6, 2 H); 7.28 (t, J ˆ 7.8, 2 H); 7.21 (t, J ˆ 6.9, 1 H); 5.61 ± 5.60( m, 1 H); 5.52 ± 5.45 (m, 3 H); 5.32 (d, J ˆ 11.7,
1 H); 4.98 (d, J ˆ 11.7, 1 H); 4.80( d, J ˆ 7.8, 1 H); 4.75 ± 4.71 (m, 2 H); 4.59 ± 4.58 (m, 1 H); 4.47 (d, J ˆ 2.8,
1 H); 4.41 ± 4.34 (m, 2 H); 4.18 ± 4.15 (m, 3 H); 4.10± 4.08 ( m, 1 H); 3.95 (t, J ˆ 5.6, 1 H); 3.64 ± 3.61 (m, 2 H);
2.59 ± 2.56 (m, 2 H); 2.31 ± 2.30( m, 1 H); 2.16 ± 2.09 (m, 6 H); 1.94 ± 1.92 (m, 2 H); 1.64 ± 1.58 (m, 1 H); 1.45 ±
1.15 (m, 53 H); 0.85 (t, J ˆ 6.9, 6 H); 0.71 (m, 4 H); 0.67 ± 0.62 (m, 2 H); À0.21 ± À 0.25 (m, 2 H). 13C-NMR
(150MHz, C 5D5N, 300 K): 174.9; 140.2; 130.8; 130.3; 130.2; 129.7; 128.5; 128.5; 128.4; 128.4; 127.5; 105.4; 80.9;
77.0; 74.9; 74.4; 71.9; 71.2; 70.4; 69.8; 67.8; 62.2; 54.3; 35.9; 34.5; 32.1; 32.1; 30.6; 30.6; 30.2; 30.2; 30.1; 30.0 (6 C);
29.9; 29.9; 29.6; 29.6; 29.0; 29.0; 28.9; 28.9; 27.8; 27.7; 27.7; 26.7; 23.9; 22.9; 22.9; 16.2; 16.2; 16.2; 16.1; 14.3; 14.3;
‡
‡
11.4; 11.4. HR-MS (MALDI-FT): 1018.7735 ([M ‡ Na] , C61H105NNaO9 ; calc. 1018.7687).
(2R,5Z)-10-[(1R,2S)-2-Decylcyclopropyl]-N-((1S,2R,6Z)-11-[(1R,2S)-2-decylcyclopropyl]-2-hydroxy-1-{[3-
O-(prop-2-enyl)-b-d-galactopyranosyloxy]methyl}undec-6-enyl)-2-hydroxydec-5-enamide (10). Amorphous
solid. Rf 0.41 (silica gel; 7% MeOH in CH2Cl2). 1H-NMR (500 MHz, CDCl3, 293 K): 7.32 (d, J ˆ 7.7, NH ) ;
5.42 ± 5.29 (m, 5 H); 4.26 (d, J ˆ 7.7, 1 H); 4.20± 4.17 ( m, 1 H); 4.14 ± 4.11 (m, 2 H); 4.05 ± 3.85 (m, 5 H); 3.81 ±
3.79 (m, 1 H); 3.69 ± 3.65 (m, 2 H); 3.48 (m, 1 H); 3.37 (br. s, 1 H); 3.28 (dd, J ˆ 3.3, 9.6, 1 H); 3.17 (br. s, 2 H);
2.94 (br. s, 1 H); 2.19 ± 2.16 (m, 2 H); 2.04 ± 1.98 (m, 4 H); 1.86 ± 1.83 (m, 1 H); 1.74 (s, 3 H); 1.66 (s, 3 H); 1.56 ±
1.45 (m, 3 H); 1.40± 1.11 ( m, 49 H); 1.11 ± 1.01 (m, 4 H); 0.86 (t, J ˆ 7.0, 6 H); 0.63 ± 0.61 (m, 4 H); 0.56 ± 0.52
‡
‡
(m, 2 H); À0.26 ± À 0.29 (m, 2 H). HR-MS (FAB): 1106.7045 ([M ‡ Cs] , C59H107CsNO9 ; calc. 1106.7000).
Preparation of Stock Solutions of Test Compounds. For all biological experiments, stock solns. of the
plakosides were prepared in DMSO at 10m m concentration. The highest concentration tested was 50 mm. The
reference compounds cyclosporine A (CsA) and azathioprine were dissolved in EtOH and DMSO at 1 mm and
2 mm, resp.
Allogeneic Mixed Lymphocyte Reaction (MLR). The two-way MLR was performed according to standard
procedures [27][29] and has been described in [29]. Briefly, spleen cells from CBA and BALB/c mice (1.6 Â 105
cells from each strain per well in flat bottom tissue culture microtiter plates, 3.2 Â 105 in total) were incubated in
RPMI medium containing 10% FCS, 100 U/ml penicillin, 100 mg/ml streptomycin (Gibco BRL, Basel,
Switzerland), 50 mm 2-mercaptoethanol (Fluka, Buchs, Switzerland), and serially diluted compounds. Seven
fivefold dilution steps in duplicates per test compound were performed. After 4 days of incubation 1 mCi
[3H]thymidine was added. Cells were harvested after an additional 5-h incubation period, and incorporated
[3H]thymidine was determined according to standard procedures. Background values (low control) of the MLR
were the proliferation of BALB/c cells alone.
Concanavalin A (Con A) Response. The Con A response with mouse spleen cells was performed according
to standard procedures [30]. Briefly, spleen cells from CBA mice (2 Â 105 cells per well) were incubated for 2
days in RPMI medium as described above. Cells were stimulated with 2 mg/ml Con A (Boehringer, Mannheim,
Germany). Compounds were tested and proliferation was assessed as described for the MLR. Background
values were the proliferation of cells in the absence of Con A.

Helvetica Chimica Acta ± Vol. 83 (2000)
2005
Murine Bone Marrow Cell Proliferation Assay. Bone marrow cells from CBA mice (2.5 Â 104 cells per well)
were incubated for 4 days in 100 ml RPMI medium. WEHI-3-Conditioned medium (7.5% (v/v)) and L929-
conditioned medium (3% (v/v)) were added as a source of growth factors. Compounds were tested and
proliferation was assessed as described above. Conditioned media were prepared as follows. WEHI-3 Cells
(ATCC TIB68) and L929 cells (ATCC CCL 1) were grown in RPMI medium until confluence for 4 days and one
week, resp. Cells were harvested, resuspended in the same culture flasks in medium C containing 1% FCS [31],
and incubated for 2 days (WEHI-3) or one week (L929). The supernatant was collected, filtered through 0.2 mm
and stored in aliquots at À808. Cultures without test compounds and without WEHI-3 and L929 supernatants
were used as low controls.
Data Analysis. Low controls were subtracted from all values. High controls without any sample were taken
as 100% proliferation. Percent inhibition by the samples was calculated, and the concentrations required for
50% inhibition (IC50 values) were determined using a four parameter logistic function.
We thank Drs. Gary Siuzdak and Dee H. Huang for mass spectrometry and NMR assistance, respectively,
and Dr. David Lo for the insightful discussions on immunosuppression. The excellent technical assistance of
Ulrike Strittmatter with respect to the biological evaluation of the plakosides is greatly acknowledged. This work
was financially supported by the National Institute of Health (USA), The Skaggs Institute for Chemical Biology,
and grants from Pfizer, Schering Plough, F. Hoffmann-La Roche, Merck, Abbott Laboratories, Boehringer
Ingelheim, Glaxo, and DuPont.
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Received February 18, 2000