Stereoselective synthesis of differentially protected derivatives of the higher amino sugars destomic acid and lincosamine from serine and threonine

Article abstract of DOI:10.1021/jo9517914

The aminoheptose destomic acid (3.5) and the aminooctose lincosamine (6.8) were synthesized in protected form by parallel sequences starting from the oxazolidine derivatives 2.4 and 5.1 of N-CBz serinal and N-BOC threoninal. The parallel sequences feature

Full text of DOI:10.1021/jo9517914

J . Org. Chem. 1996, 61, 581-586
581
Ster eoselective Syn th esis of Differ en tia lly P r otected Der iva tives
of th e High er Am in o Su ga r s Destom ic Acid a n d Lin cosa m in e fr om
Ser in e a n d Th r eon in e
J ames A. Marshall* and Serge Beaudoin
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22903
Received October 2, 1995X
The aminoheptose destomic acid (3.5) and the aminooctose lincosamine (6.8) were synthesized in
protected form by parallel sequences starting from the oxazolidine derivatives 2.4 and 5.1 of N-CBz
serinal and N-BOC threoninal. The parallel sequences feature BF3-promoted addition of the (R)-
γ-OTBS allylic stannane 2.8 to the homologated enals 2.7 and 5.4, respectively, followed by
stereoselective bis-dihydroxylation of the derived bis-OTBS ethers 2.10 and 5.6. Regioselective
oxidative cleavage of the less hindered vicinal diol moieties of these intermediates led to the γ-lactols
3.2 and 5.8, respectively. In the former case, treatment with TBAF and subsequent hydrolysis
removed the OTBS and acetonide protecting groups affording the destomic acid precursor, pyranose
3.4. Lactol 5.8 was converted to the pyranoside 6.3 by silyl ether cleavage, acidic hydrolysis, and
bis-acetonide formation. Inversion of the C7 hydroxyl grouping was effected by the Mitsunobu
methodology with p-NO2C6H4CO2H. Subsequent hydrolysis, cleavage of the BOC grouping, and
N-acetylation afforded the lincosamine derivative 6.7.
We recently described a sequence for the conversion
of conjugated enals 1.1 to syn,anti, syn,anti,syn polyol
derivatives 1.8 and their subsequent oxidative cleavage
to carbohydrate γ-lactols 1.10 (eq 1).1 The key elements
of this approach are (1) highly syn selective addition of
the enantioenriched γ-silyloxy allylic stannane 1.3 to the
aforementioned enals 1.1, (2) highly anti selective bis-
dihydroxylation of the bis-TBS ethers 1.5 of these ad-
ducts, and (3) regioselective oxidative cleavage of the
derived tetrols 1.8 at the more accessible 1,2-diol termi-
nus, attended by in situ internal protection of the
surviving, less reactive, 1,2-diol function through lactol
formation.
protecting groups) from readily available R-amino acids.4
It was of particular interest to assess the effect of a pro-
tected allylic amine function on the diastereoselectivity
of the hydroxylation step 1.7 f 1.9 and the regioselec-
tivity of the subsequent oxidative cleavage 1.9 f 1.11.
As the first synthetic target of these studies we chose
destomic acid (3.5), an aminohepturonic acid component
of the destomycin and hygromycin antibiotics.5 Our
starting material for this project was the Cbz analogue
2.4 of the so-called Garner aldehyde, derived from N-Cbz
L-serine (2.1) by esterification, oxazolidine formation, and
reduction.6 Horner-Emmons condensation with triethyl
phosphonoacetate led to the (E)-conjugated ester 2.5
which was subjected to the usual sequential reduction-
oxidation sequence to yield enal 2.7. BF3-promoted
addition of the (R)-OTBS allylic stannane 2.8 afforded
the syn adduct 2.9 in high yield as a single diastereoi-
somer. Conversion to the bis-TBS ether 2.10 was effected
in near-quantitative yield with TBSOTf and 2,6-lutidine.
These preliminary studies were conducted with enals
prepared from protected D-erythrose and D-arabinose
leading, in the former case, to “D-R,R-galaoctonic lactone”,
a galactose homologue, first prepared by Fischer in 1895,2
and in the latter case, an 11-carbon polyol intermediate
employed by Schreiber and Ikemoto in their synthesis
of the antibiotic hikizimycin.3 Our current studies were
undertaken to test the applicability of this methodology
(4) Cf. J urczak, J .; Golebiowski, A. Chem. Rev. 1989, 89, 149. Reetz,
M. T. Angew. Chem., Int. Ed. Engl. 1991, 30, 1531. Dondoni, A.;
Perrone, D. J . Org. Chem. 1995, 60, 4794.
(5) (a) For a previous synthesis from D-galactose, see Hashimoto,
H.; Asano, K.; Fujii, F.; Yoshimura, J . Carbohydr. Res. 1982, 104, 87.
(b) For a recent approach see Golebiowski, A.; Kozak, J .; J urczak, J .
J . Org. Chem. 1991, 56, 7344. (c) Dondoni, A.; Franco, S.; Merchan,
F.; Merino, P.; Tejero, T. Synlett 1993, 78.
to the synthesis of higher amino sugars 1.11 (P1, P2
)
X Abstract published in Advance ACS Abstracts, J anuary 1, 1996.
(1) (a) Marshall, J . A.; Beaudoin, S. J . Org. Chem. 1994, 59, 6614.
(b) Marshall, J . A.; Beaudoin, S. J . Org. Chem. 1994, 59, 7833.
(2) Fischer, E. Liebigs Ann. Chem. 1895, 288, 150.
(6) (a) Garner, P.; Park, J .-M. J . Org. Chem. 1987, 52, 2361. (b)
Garner, P.; Park, J .-M. Org. Synth. 1991, 70, 18. (c) McKillop, A.;
Taylor, R. J . K.; Watson, R. J .; Lewis, N. Synthesis 1994, 31.
(3) Ikemoto, N.; Schreiber, S. J . Am. Chem. Soc. 1992, 114, 2524.
0022-3263/96/1961-0581$12.00/0 © 1996 American Chemical Society

582 J . Org. Chem., Vol. 61, No. 2, 1996
Marshall and Beaudoin
We were now in a position to evaluate the effect of the
terminal oxazoline ring on the diastereoselectivity of the
hydroxylation reaction. If the bis-OTBS diene 2.10
adopts the Saito conformation, as depicted in eq 3, we
would expect addition to occur mainly anti to the OTBS
substituents.7 In fact, when diene 2.10 was treated with
an excess of NMO in the presence of catalytic OsO4,8 a
major tetrol product, presumably 3.1, was isolated in 68%
yield after separation from minor diastereomeric impuri-
ties. Allylic ethers tend to give anti dihydroxylation
products, whereas allylic amine amides show modest to
negligible directing effects on double bond additions.9,10
Thus, it is not surprising that direction by the OTBS
grouping is the dominant factor in the present case.
the thioglycoside and the parent pyranose have been
reported. These fall into two main groups. The earliest
approaches start from a galactose derived aldehyde 4.1
and introduce the additional two carbons.12 Although
conceptually simple these routes suffer from excessive
protecting group manipulations and lack of stereocontrol.
A recent synthesis along these lines by Knapp and
Kukkola is an exception.12h Danishefsky, employing his
diene/aldehyde cyclocondensation strategy, prepared ra-
cemic peracetyl â-methylincosaminide.13a-c Of special
interest in this pioneering work, and the later studies of
Knapp, is the stereocontrolled introduction of the C6/C7
amino alcohol array through functionalization of a C5
propenylated pyranoside.
In recent years several groups have described routes
to lincosamine and analogues starting from a protected
C5-C8 amino alcohol segment 4.3 (P, P1, P2 ) protecting
groups) derived from D-allothreonine.13d-f Clearly this
approach is well suited to the studies at hand. However
we chose the epimeric aldehyde 5.1,6 available from
D-threonine, as a starting material over the seemingly
more appropriate allothreonine counterpart 4.3. We felt
that the lower cost and greater stability of aldehyde 5.1
outweighed the possible disadvantage of the requisite
later stage inversion at C7 (see 4.2).
Horner-Emmons homologation14 of aldehyde 5.1 pro-
ceeded smoothly, and the resulting (E) conjugated ester
was transformed by successive reduction-oxidation to
the enal 5.4. BF3-promoted addition of the (R)-silyloxy
allylic stannane 2.8 gave the syn adduct 5.5 as the sole
product.1a The derived bis-TBS ether 5.6 was bis-
The selective oxidative cleavage of tetrol 3.1 proceeded
smoothly to afford lactol 3.2 in 81% yield. Desilylation
followed by acetonide hydrolysis afforded the pyranose
derivative 3.4, an intermediate in Hashimoto's synthesis
of destomic acid from galactose.5a For the purpose of
characterization, pyranose 3.4, a mixture of R- and
â-anomers, was converted to the known bis-acetonide
3.6.5 A small amount of the oxazolidine 3.7 was also
formed in this reaction. The 1H NMR spectrum and
optical rotation of 3.6 were in excellent accord with the
reported values.5
The second synthetic target of interest, lincosamine
(6.8), is an amino octose component of lincomycin, a
Gram-positive glycopeptide antibiotic which was struc-
turally elucidated by workers at Upjohn in the 1960s.11
Crucial to this elucidation was the finding that, upon
hydrazinolysis, lincomycin is converted to methyl thi-
olincosaminide (4.2) and trans-1-methyl-4-propyl-L-pro-
line. In subsequent years numerous synthetic routes to
8
dihydroxylated with NMO and catalytic OsO4 to the
tetrol 5.7 as the major product. With diene 5.6, the allylic
amide function may reinforce the OTBS groupings in
directing the dihydroxylation step but the effect is
modest, at best.
Selective oxidative cleavage of the more accessible
vicinal diol of 5.7 was effected in high yield. However,
subsequent conversion of the resulting lactol 5.8 to
pyranoside 6.2 proceeded in less than 30% yield under a
variety of conditions . A considerable improvement was
realized by performing this reaction on the deprotected
lactol 6.1. In this way, a 55:45 mixture of acetonides 6.2
and 6.3 was realized in 56% yield. The former was
(12) (a) Magerlein, B. J . Tetrahedron Lett. 1970, 33. (b) Howarth,
G. B.; Szarek, W. A.; J ones, J . K. N. J . Chem. Soc. (C) 1970, 2218. (c)
Saeki, S.; Ohki, E. Chem. Pharm. Bull. 1970, 18, 789. (d) Fukumaru,
T.; Atsumi, T.; Ogawa, T.; Matsui, M. Agr. Biol. Chem. 1973, 37, 2617.
(e) Woolard, G. R.; Rathbone, E. B.; Szarek, W. A.; J ones, J . K. N. J .
Chem. Soc. Perkin Trans.
1 1976, 950. (f) Gateau-Olesker, A.;
(7) Cf. (a) Saito, S.; Narahara, O.; Ishikawa, T.; Asahara, M.;
Moriwake, T.; Gawronski, J .; Kazimiercyzk, F. J . Org. Chem. 1993,
58, 6292. (b) Gung, B. W.; Melnick, J . P.; Wolf, M. A.; Marshall, J . A.
Beaudoin, S. J . Org. Chem. 1994, 59, 5609.
(8) VanRheenen, V.; Kelly, R. C.; Chas, D. Y. Tetrahedron Lett. 1976,
1973.
(9) Cf. (a) Cha, J . K.; Christ, W. J .; Kishi, Y. Tetrahedron Lett. 1983,
24, 3947. (b) Stork, G.; Kahn, M. Tetrahedron Lett. 1983, 24, 3951.
(10) (a) Cf. Krysan, D. J .; Rockway, T. W.; Haight, A. R. Tetrahedron
Asymmetry 1994, 5, 625 and references therein. (b) For a recent review,
see Cha, J . K.; Kim, N.-S. Chem. Rev. 1995, 95, 1761.
(11) Slomp, G.; MacKellar, F. A. J . Am. Chem. Soc. 1967, 89, 2454.
Sepulchre, A. M.; Vass, G.; G´ıro, S. D. Tetrahedron 1977, 33, 393. (g)
Hoppe, I.; Scho¨llkopf, U. Liebigs Ann. Chem. 1980, 1474. (h) Knapp,
S.; Kukkola, P. J . J . Org. Chem. 1990, 55 1632.
(13) (a) Larson, E. R.; Danishefsky, S. J . Am. Chem. Soc. 1983, 105,
6715. (b) Danishefsky, S.; Larson, E.; Springer, J . P. J . Am. Chem.
Soc. 1985, 107, 1274. (c) Danishefsky, S.; DeNinno, M. P.; Schulte, G.
J . Org. Chem. 1987, 52, 3173. (d) Golebiowski, A.; J urczak, J .;
Krajewski, J . W.; Galilskii, N. M.; Vernich, A. J . Bull. Polish Acad.
Sci. 1989, 37, 307. (e) Golebiowski, A.; J urczak, J . Tetrahedron 1991,
47, 1045. (f) Szechner, B.; Achmatowicz, O. J . Carbohydrate Chem.
1992, 11, 401.
(14) Wadsworth, W. S., J r. Org. React. 1977, 25, 73.

Synthesis of Destomic Acid and Lincosamine Derivatives
J . Org. Chem., Vol. 61, No. 2, 1996 583
protecting group. Acetylation of the resulting amine 6.6
1
afforded the known acetamide 6.7. The H NMR spec-
trum and optical rotation of this material closely matched
the reported values.
It is clear from the foregoing results that protected
R-amino aldehydes are suitable substrates for our previ-
ously described carbohydrate homologation sequence.1 In
the current studies we have employed methodology that
favors syn adducts of the enal intermediates 2.7 and 5.4.
Recent findings that indium analogues of the enantioen-
riched stannane 2.8, prepared in situ, afford anti adducts
with enals extends the potential scope of this methodol-
ogy.16
Exp er im en ta l Section 17
N-(Ben zyloxyca r bon yl)-L-Ser in e, Meth yl Ester (2.2).
To a solution of acid 2.1 (4.91 g, 20.5 mmol) in MeOH (40 mL)
at 0 °C was added 2.3 mL (31.5 mmol) of SOCl2 (caution heat
and HCl are evolved!). After being stirred at rt for 24 h, the
reaction mixture was concentrated under reduced pressure.
The residue was dissolved in Et2O, washed with saturated
NaHCO3, and dried over Na2SO4 to give the ester 2.1 (4.93 g,
95%) as a yellow oil: [R]D +8.5 (c 1.19, CHCl3); IR 3404, 1714;
1H NMR (400 MHz) δ 2.25 (1 H, bs), 3.76 (3 H, s), 3.94 (2 H,
bd, J ) 19.2 Hz), 4.43 (1 H, bs), 5.11 (2 H, s), 5.70 (1 H, bs),
7.28-7.35 (5 H, m). Anal. Calcd for C12H15NO5: C; 56.91, H;
5.97, N; 5.53. Found: C; 56.65, H; 5.91, N; 5.46.
smoothly converted to the latter by exposure to acidic
methanol. These findings suggest that the oxazolidine
function of lactol 5.8 in some way interferes with pyra-
noside formation. Unfortunately we were not able to
isolate descrete intermediates that could shed light on
the sequence of events leading to pyranoside 6.2.
(S)-Meth yl 3-(Ben zyloxyca r bon yl)-2,2-d im eth yloxa zo-
lid in e-4-ca r boxyla te (2.3). To a solution of ester 2.2 (4.80
g, 19.0 mmol) in acetone (68 mL) and 2,2-dimethoxypropane
(20 mL) was added 0.13 mL (1.06 mmol) of BF3‚OEt2. After
25 h, the reaction mixture was concentrated under reduced
pressure. The residue was dissolved in CH2Cl2, washed with
1:1 saturated NaHCO3-H2O and brine, and dried over Na2SO4.
Purification by flash chromatography on silica gel (1:1, hex-
anes-Et2O) gave oxazolidine 2.3 (5.28 g, 95%): [R]D -51.9 (c
1.06, CHCl3); IR 1758, 1716; 1H NMR δ (C6D6, 70 °C): 1.54 (3
H, s), 1.85 (3 H, s), 3.25 (3 H, s), 3.69 (1 H, dd, J ) 7.0, 9.0
Hz), 3.82 (1 H, dd, J ) 2.8, 9.0 Hz), 4.26 and 4.45 (1 H, bs),
4.98 and 5.12 (2 H, ABq, J ) 12.5 Hz), 7.03-7.20 (5 H, m).
Anal. Calcd for C15H19NO5: C; 61.42, H; 6.53, N; 4.78.
Found: C; 61.48, H; 6.55, N; 4.78.
(S)-3-(Ben zyloxyca r b on yl)-4-for m yl-2,2-d im et h ylox-
a zolid in e (2.4). To a solution of ester 2.3 (5.08 g, 17.3 mmol)
in PhCH3 (35 mL) at -78 °C was added 20 mL (30.0 mmol) of
1.5 M DIBAL-H in PhCH3. After 2 h, an additional 7 mL (10.5
mmol) of 1.5 M DIBAL-H in PhCH3 was added and after 1 h,
another 7 mL (10.5 mmol) portion was added. Stirring was
continued for 1 h, and the reaction mixture was quenched with
MeOH (11.6 mL) followed by aqueous potassium sodium
tartrate and allowed to warm to rt. After being stirred for 3
h, the aqueous phase was extracted with Et2O, and the
combined organic extracts were dried over Na2SO4. Purifica-
tion by flash chromatography on silica gel (4:6, hexanes-Et2O)
gave aldehyde 2.4 (3.42 g, 75%): [R]D -63.7 (c 1.23, CHCl3);
1
IR 2886, 2819, 1713; H NMR (C6D6, 70 °C): δ 1.42 (3 H, s),
1.60 (3 H, s), 3.45 (1 H, dd, J ) 7.2, 9.3 Hz), 3.64 (1 H, dd, J
) 2.0, 9.3 Hz), 3.86 (1 H, bs), 5.00 (2 H, s), 7.04-7.16 (5 H,
m), 9.24 (1 H, bs). Anal. Calcd for C14H17NO4: C; 63.87, H;
6.51, N; 5.32. Found: C; 63.76, H; 6.48, N; 5.27.
(R)-3-(Ben zyloxyca r b on yl)-2,2-d im et h yl-4-[(E)-2-ca r -
bom eth oxyvin yl]oxa zolid in e (2.5). To a suspension of NaH
(338 mg, 14.1 mmol) in THF (25 mL) at 0 °C was added 2.9
mL (14.6 mmol) of triethyl phosphonoacetate. After 30 min,
aldehyde 2.4 (3.13 g, 11.9 mmol) in THF (25 mL) was added
dropwise. After being stirred for 1 h, the reaction mixture was
quenched with H2O, diluted with Et2O, washed with brine,
Inversion of the C7 carbinyl center was effected by the
methodology of Mitsunobu. For this conversion, p-
nitrobenzoic acid15 proved superior to benzoic acid in both
purity of the derived ester 6.4 and ease of its subsequent
cleavage with methanolic KCN. The inverted alcohol 6.5
was treated with trifluoroacetic acid to remove the BOC
(16) Marshall, J . A.; Hinkle, K. W. J . Org. Chem. 1995, 60, 1920.
(17) Unless otherwise indicated 1HNMR spectra were recorded at
300 MHz in CDCl3. Infrared spectra were determined as thin films
and are reported in cm-1. For a summary of experimental protocols,
see Marshall, J . A.; Wang, X.-J . J . Org. Chem. 1991, 56, 960.
(15) Martin, S. F.; Dodge, J . A. Tetrahedron Lett. 1991, 32, 3107.
Dodge, J . A.; Trujillo, J . I.; Presnell, M. J . Org. Chem. 1994, 59, 234.

584 J . Org. Chem., Vol. 61, No. 2, 1996
Marshall and Beaudoin
and dried over Na2SO4. Purification by flash chromatography
4.35 (3 H, m), 5.07 (1 H, d, J ) 12.4 Hz), 5.15-5.20 (1 H, m),
5.60-5.90 (4 H, m), 7.30-7.35 (5 H, m). Anal. Calcd for
C32H55NO5Si2: C; 65.15, H; 9.40, N; 2.37. Found: C; 65.25,
H; 9.36, N; 2.39.
on silica gel (7:3, hexanes-Et2O) gave ester 2.5 (3.11 g, 79%):
1
[R]D -62.5 (c 1.34, CHCl3); IR 1708, 1662; H NMR (C6D6, 70
°C) δ 1.00 (3 H, t, J ) 7.1 Hz), 1.45 (3 H, s), 1.59 (3 H, s), 3.33
(AB, 1 H, dd, J ) 2.5, 9.1Hz) , 3.53 (AB, 1 H, dd, J ) 6.4,
9.1Hz), 4.02 (2 H, q, J ) 7.1 Hz), 4.12 and 4.34 (1 H, bs and d,
J ) 5.1 Hz), 4.96 and 5.04 (2 H, AB, J )12.3 Hz), 5.95 (1 H,
bd, J ) 15.6 Hz), 6.90 (1 H, dd, J )7.0, 15.6 Hz), 7.05-7.20 (5
H, m). Anal. Calcd for C18H23NO5: C; 64.85, H; 6.95, N; 4.20.
Found: C; 64.88, H; 6.96, N; 4.10.
( R ) -3 -( B e n z y l o x y c a r b o n y l ) -2 , 2 -d i m e t h y l -4 -
[(1R,2S,3S,4S,5S,6R)-3,4-b is-[(ter t-b u t yld im et h ylsilyl)-
oxy]-1,2,5,6-tetr a h yd r oxyl]oxa zolid in e (3.1). To a solution
of diene 2.10 (1.57 g, 2.66 mmol) in Me2CO (27 mL) and H2O
(7 mL) was added 1.56 g (13.2 mmol) of NMO followed by 2.6
mL (0.24 mmol) of 2.5% OsO4 in t-BuOH. After 22 h, saturated
NaHSO3 was added. After being stirred for 30 min, the
reaction mixture was concentrated under reduced pressure.
The aqueous phase was extracted with CH2Cl2 and dried over
MgSO4. Purification by flash chromatography on silica gel (2:
1, Et2O-hexanes) gave tetrol 3.1 (1.18 g, 68%) as a waxy solid
and a faster eluting inseparable mixture of isomers (165 mg,
9%). 3.1: [R]D -46.7 (c 0.66, CHCl3); IR 3466, 1710; 1H NMR
(DMSO-d6, 74 °C) δ 0.10 (3 H, s), 0.11 (3 H, s), 0.12 (3 H, s),
0.13 (3 H, s), 0.88 (9 H, s), 0.89 (9 H, s), 1.09 (3 H, d, J ) 6.2
Hz), 1.13 (3 H, s), 1.16 (3 H, s), 3.29 (1 H, t, J ) 8.5 Hz), 3.49-
4.06 (11 H, m), 4.23 (1 H, dd, J ) 5.0, 8.6 Hz), 5.08 (1 H, d, J
) 12.6 Hz), 5.16 (1 H, d, J ) 12.6 Hz), 7.31-7.40 (5 H, m).
Anal. Calcd for C32H59NO9Si2: C; 58.41, H; 9.04, N; 2.13.
Found: C; 58.46, H; 9.03, N; 2.12.
Silyla ted La ctol 3.2. To a solution of tetrol 3.1 (1.02 g,
1.55 mmol) in THF (15 mL) at 0 °C was added 396 mg (1.74
mmol) of H5IO6. After 30 min, the reaction mixture was
diluted with Et2O, washed with saturated NaHCO3, H2O, and
brine, and dried over MgSO4. Purification by flash chroma-
tography on silica gel (1:1, Et2O-hexanes) gave lactol 3.2 (766
mg, 81%) as a glassy solid: [R]D -17.3 (c 1.31, CHCl3). Anal.
Calcd for C30H53NO8Si2: C; 58.86, H; 8.34, N; 2.15. Found:
C; 58.63, H; 8.46, N; 2.26.
6-[N-(Ca r b ob en zyloxy)a m in o]-6-d eoxy-L-glycer o-r-D-
ga la cto-h ep top yr a n ose (3.4). To a solution of lactol 3.2 (600
mg. 0.98 mmol) in THF (6 mL) was added 2.5 mL (2.5 mmol)
of 1.0 M TBAF in THF followed by 0.15 mL (2.62 mmol) of
acetic acid. After 24 h, the reaction mixture was concentrated
under reduced pressure. Purification by flash chromatography
on silica gel (95:5, EtOAc-MeOH) gave furanose 3.3 (323 mg,
86%) as a glassy solid. A solution of this oxazolidine furanose
(254 mg, 0.66 mmol) in 9:1 AcOH-H2O (1 mL) was heated at
50 °C for 1.5 h and concentrated under reduced pressure.
Residual HOAc was removed by codistillation with PhCH3
affording pyranose 3.4 (221 mg, 97%) as a white solid: mp
164-166 °C after recrystallization from MeOH [lit.5b 170-173
°C (dec)]; [R]D +32.8 (c 0.91, H2O), [lit.5b +52.9 (c 1.0, H2O)];
1H NMR (D2O) δ 3.45-4.05 (7 H, m), 4.50 (0.6 H, d, J ) 7.8
Hz), 5.12 (2 H, s), 5.20 (0.4 H, bs), 7.42 (5 H, s).
(R)-3-(Ben zyloxyca r b on yl)-2,2-d im et h yl-4-[(E)-3-h y-
d r oxy-1-p r op en yl]oxa zolid in e (2.6). To a solution of ester
2.5 (2.93 g, 8.79 mmol) in THF (26 mL) at -78 °C was added
32 mL (32.0 mmol) of 1.0 M DIBAL-H in hexanes. After 2 h,
the reaction mixture was quenched with saturated Rochelle's
salt and warmed to rt. After being stirred for 3 h, the aqueous
phase was extracted with Et2O, and the combined organic
extracts were dried over MgSO4. Purification by flash chro-
matography on silica gel (3:1 Et2O-hexanes) gave alcohol 2.6
(2.03 g, 79%) as a colorless oil: [R]D -13.2 (c 1.16, CHCl3); IR
1
3457, 1698; H NMR (DMSO-d6, 85 °C): δ 1.47 (3 H, s), 1.54
(3 H, s), 3.10 (1 H, bs), 3.72 (1 H, dd, J ) 2.3, 8.9 Hz), 3.93 (2
H, d, J )2.9 Hz), 4.05 (1 H, dd, J ) 6.1, 8.9 Hz), 4.43 (1 H, bs),
5.05 and 5.11 (2 H, ABq, J ) 12.7 Hz), 5.63-5.67 (2 H, m),
7.32-7.38 (5 H, m). Anal. Calcd for C16H21NO4: C; 65.96, H;
7.27, N; 4.81. Found: C; 65.71, H; 7.32, N; 4.78.
(R )-3-(B e n zy lo x y c a r b o n y l)-2,2-d im e t h y l-4-[(E )-2-
for m ylvin yl]oxa zolid in e (2.7). To a solution of oxalyl
chloride (0.67 mL, 7.68 mmol) in CH2Cl2 (20 mL) at
-78 °C was added 1.1 mL (20.8 mmol) of DMSO. After 5 min,
alcohol 2.6 (1.94 g, 6.6 mmol) in CH2Cl2 (20 mL) was added
dropwise. After 15 min, Et3N (4.6 mL, 33.0 mmol) was added.
After being stirred at 0 °C for 30 min, the reaction mixture
was washed with H2O, 10% HCl, saturated NaHCO3, H2O, and
brine, and dried over MgSO4. Purification by flash chroma-
tography on silica gel (2:1, Et2O-hexanes) gave aldehyde 2.7
(1.73 g, 90%): [R]D -62.8 (c 1.09, CHCl3); IR 2821, 2725, 1694;
1H NMR (DMSO-d6, 85 °C) δ 1.51 (3 H, s), 1.57 (3 H, s), 3.88
(1 H, dd, J ) 2.4, 9.3 Hz), 4.17 (1 H, dd, J ) 6.6, 9.3 Hz), 4.70-
4.75 (1 H, m), 5.07 and 5.14 (2 H, ABq, J ) 12.5 Hz), 6.07 (1
H, dd, J ) 7.6, 15.6 Hz), 6.94 (1 H, dd, J ) 6.3, 15.6 Hz), 7.30-
7.35 (5 H, m), 9.55 (1 H, d, J ) 7.6 Hz). Anal. Calcd for C16H19
-
NO4: C; 66.42, H; 6.62 N; 4.79. Found: C; 66.16, H; 6.56, N;
4.79.
( R ) -3 -( B e n z y l o x y c a r b o n y l ) -2 , 2 -d i m e t h y l -4 -
[(1E,5E,3S,4S)-4-[(ter t-bu tyldim eth ylsilyl)oxy]-3-h ydr oxy-
1,5-h ep ta d ien yl]oxa zolid in e (2.9). To a solution of aldehyde
2.7 (1.06 g, 3.66 mmol) and (R)-stannane 2.8 (2.26 g, 4.75
mmol) in CH2Cl2 (25 mL) was added 0.6 mL (4.9 mmol) of
BF3‚OEt2. After 2 h, the reaction mixture was quenched with
saturated NaHCO3, allowed to warm to rt, diluted with Et2O,
washed with H2O and brine, and dried over MgSO4. Purifica-
tion by flash chromatography on silica gel (1:1, hexanes-Et2O)
gave alcohol 2.9 (1.51 g, 87%): [R]D -20.6 (c 1.43, CHCl3); IR
3490, 1708; 1H NMR (DMSO-d6, 85 °C) δ 0.02 (3 H, s), 0.04 (3
H, s), 0.87 (9 H, s), 1.46 (3 H, s), 1.54 (3 H, s), 1.60 (3 H, d, J
) 6.3 Hz), 3.68 (1 H, dd, J ) 2.1, 8.8 Hz), 3.87-3.91 (1 H, m),
3.96-4.00 (1 H, m), 4.05 (1 H, dd, J ) 6.1, 8.8 Hz), 4.43-4.45
(1 H, m), 5.03, 5.11 (ABq, J ) 12.7 Hz), 5.38 (1 H, ddq, J )
1.4, 6.3, 15.4 Hz), 5.48-5.70 (3 H, m), 7.30-7.35 (5 H, m). Anal.
Calcd for C26H41NO5Si: C; 65.65, H; 8.69, N; 2.94. Found: C;
65.47, H; 8.65, N; 2.93.
1,2:3,4-Di-O-isopr op yliden e-6-[N-(ca r boben zyloxy)a m i-
n o]-6-d eoxy-L-glycer o-r-D-ga la cto-h ep top yr a n ose (3.6).
To a solution of pyranose 3.4 (40 mg, 0.12 mmol) in anhydrous
Me2CO (0.5 mL) was added 47 mg (0.29 mmol) of CuSO4
followed by 2 µL (0.13 mmol) of concd H2SO4. After being
stirred for 16 h, the reaction mixture was filtered. The filtrate
was neutralized with Ca(OH)2 (23 mg, 0.31 mmol) and filtered
through Celite and then concentrated under reduced pressure.
Purification by flash chromatography on silica gel (1:1 then
3:1 Et2O-hexanes) gave the pyranoside diacetonide 3.6 (23
mg, 46%) as a glassy solid and oxazolidine 3.7 (14 mg, 26%).
3.6: [R]D -47.1 (c 0.72, CHCl3), [lit. -47.3 (c 0.2, CHCl3),5a
1
-48.8 (c 2, CHCl3)5b]; H NMR δ 1.32 (6 H, s), 1.42 (3 H, s),
1.51 (3 H, s), 3.22 (1 H, bs), 3.70-3.90 (3 H, m), 4.10 (1 H, bd,
J ) 5.8 Hz), 4.30 (1 H, dd, J ) 1.5, 8.0 Hz), 4.35 (1 H, dd, J )
1.5, 8.0 Hz), 4.62 (1 H, dd, J ) 2.3, 8.0 Hz), 5.11 (2 H, s), 5.40-
5.50 (1 H, m), 5.52 (1 H, d, J ) 5.0 Hz), 7.26-7.36 (5 H, m).
3.7: IR 1703; 1H NMR (DMSO-d6, 85 °C) 1.27 (9 H, s), 1.40
(3 H, s), 1.46 (3 H, s), 1.54 (3 H, s), 3.73 (1 H, bd, J ) 9.3 Hz),
3.83 (1 H, dd, J ) 5.4, 9.2 Hz), 3.95 (1 H, d, J ) 9.1 Hz), 4.25-
4.35 (3 H, m), 4.52 (1 H, d, J ) 7.7 Hz), 4.98, 5.01 (2 H, ABq,
J ) 11.6 Hz), 5.39 (1 H, d, J ) 5.2 Hz), 7.20-7.30 (5 H, m).
(4S,5S)-3-(ter t-Bu t oxyca r b on yl)-2,2-d im et h yl-4-[(E)-
ca r bom eth oxyvin yl]-5-m eth yloxa zolid in e (5.2). The pro-
cedure described above for ester 2.5 was employed with 7.18
g (29.5 mmol) of aldehyde 5.1, 847 mg (35.3 mmol) of NaH,
and 7.0 mL (35.3 mmol) of triethyl phosphonoacetate affording
( R ) -3 -( B e n z y l o x y c a r b o n y l ) -2 , 2 -d i m e t h y l -4 -
[(1E,5E,3S,4S)-3,4-b is[(ter t-b u t yld im et h ylsilyl)oxy]-1,5-
h ep ta d ien yl]oxa zolid in e (2.10). To a solution of alcohol 2.9
(1.41 g, 2.95 mmol) in CH2Cl2 (35 mL) at 0 °C was added 0.76
mL (6.52 mmol) of 2,6-lutidine followed by 1.2 mL (5.2 mmol)
of TBSOTf. After 30 min, the reaction mixture was diluted
with Et2O, washed with H2O, 10% HCl, saturated NaHCO3,
H2O, and brine, and dried over MgSO4. Purification by flash
chromatography on silica gel (4:1, hexanes-Et2O) gave disilyl
ether 2.10 (1.68 g, 97%) as a colorless oil: [R]D -54.0 (c 1.07,
1
CHCl3); IR 1710; H NMR (DMSO-d6, 67 °C) δ 0.08 (3 H, s),
0.10 (3 H, s), 0.11 (3 H, s), 0.13 (3 H, s), 0.99 (9 H, s), 1.00 (9
H, s), 1.53 (3 H, s), 1.59 (3 H, d, J ) 4.5 Hz), 1.76 (3 H, s), 3.60
(1 H, dd, J ) 1.9, 8.7 Hz), 3.72 (1 H, dd, J ) 5.9, 8.7 Hz), 4.15-

Synthesis of Destomic Acid and Lincosamine Derivatives
J . Org. Chem., Vol. 61, No. 2, 1996 585
ester 5.2 (8.46 g, 91%) as a colorless oil: [R]D +31.2 (1.30,
and 242 mg (1.06 mmol) of H5IO6 affording lactol 5.8 (504 mg,
90%) as a solid foam: mp 55-61 °C, [R]D +48.9 (c 0.97, CHCl3);
IR 3445, 1673. Anal. Calcd for C28H57NO8Si: C; 56.82, H;
9.75, N; 2.37. Found: C; 56.85, H; 9.75, N; 2.43.
1
CHCl3), IR 1703, 1660; H NMR (DMSO-d6, 85 °C) 1.22 (3 H,
d, J ) 2.9 Hz), 1.23 (3 H, t, J ) 7.0 Hz), 1.38 (9 H, s), 1.49 (3
H, s). 1.53 (3 H, s), 3.80-4.00 (2 H, m), 4.17 (2 H, q, J ) 7.0
Hz), 5.95 (1 H, d, J ) 15.7 Hz), 6.69 (1 H, dd, J ) 7.6, 15.7
Hz). Anal. Calcd for C16H27NO5: C; 61.32, H; 8.68, N; 4.47.
Found: C; 61.03, H; 8.58, N; 4.44.
(4S,5S)-3-(ter t-Bu toxyca r bon yl)-2,2-d im eth yl-4-[(E)-3-
h yd r oxy-1-p r op en yl]-5-m eth yloxa zolid in e (5.3). The pro-
cedure described above for alcohol 2.6 was employed with 8.03
g (25.6 mmol) of ester 5.2 and 57.0 mL (57.0 mmol) of 1.0 M
DIBAL-H in hexanes affording alcohol 5.3 (8.46 g, 91%) as a
colorless oil: [R]D -6.6 (c 1.23, CHCl3); IR 3441, 1699; 1H NMR
(DMSO-d6, 85 °C): 1.20 (3 H, d, J ) 6.0 Hz), 1.39 (9 H, s),
1.45 (3 H, s), 1.51 (3 H, s), 3.70 (1 H, t, J ) 7.7 Hz), 3.78-3.86
(1 H, m), 3.97 (2 H, td, J ) 1.2, 5.1 Hz), 4.45 (1 H, td, J ) 1.1,
5.4 Hz), 5.49 (1 H, tdd, J ) 1.6, 7.7, 15.4 Hz), 5.68 (1 H, tdd,
J ) 0.6, 4.9, 15.4 Hz). Anal. Calcd for C14H25NO4: C; 61.97,
H; 9.29, N; 5.16. Found: C; 61.88, H; 9.30, N; 5.09.
6-[(ter t-Bu toxyca r bon yl)a m in o]-6,8-d id eoxy-1,2:3,4-d i-
O-isop r op ylid en e-D-th r eo-r-D-ga la cto-octop yr a n ose (6.3).
The procedure described above for pyranose 3.4 was employed
with 1.10 g (1.86 mmol) of lactol 5.8, 4.7 mL (4.7 mmol) of
1.0M TBAF in THF and 0.28 mL (4.90 mmol) of HOAc
affording pyranoside 5.9 (670 mg, 99%) of a solid foam: mp
95-100 °C. A 388-mg sample of this material was heated with
4.0 mL of 9:1 HOAc-H2O as described above affording 388 mg
of crude lactol 6.1 which was treated as described above for
diacetonide 3.6 with 5.0 mL of acetone, 480 mg of CuSO4, and
0.02 mL of H2SO4 affording diacetonide 6.3 (126 mg, 26%) and
oxazolidine 6.2 (161 mg, 30%) as a white solid.
6.2: mp 127-129 °C; [R]D +4.0 (c 1.08, CHCl3); IR (CCl4)
1
1694; H NMR δ 1.30 (6 H, s), 1.31 (3 H, d, J ) 6.3 Hz), 1.42
(3 H, s), 1.47 (12 H, s), 1.53 (3 H, s), 1.59 (3 H, s), 3.86 (1 H,
bs), 4.10-4.30 (2 H, m), 4.27 (1 H, dd, J ) 2.2, 4.9 Hz), 4.58 (1
H, dd, J ) 2.1, 3.9 Hz), 4.65 (1 H, dq, J ) 2.3, 6.3 Hz), 5.58 (1
H, d, J ) 5.0 Hz). Anal. Calcd for C22H37NO8: C; 59.58, H;
8.41, N; 3.16. Found: C; 59.66, H; 8.37, N; 3.10.
(4S,5S)-3-(ter t-Bu toxyca r bon yl)-2,2-d im eth yl-4-[(E)-2-
for m ylvin yl]-5-m eth yl oxa zolid in e (5.4). The procedure
described above for aldehyde 2.7 was employed with 2.79 g
(10.3 mmol) of alcohol 5.3, 1.0 mL (11.5 mmol) of oxalyl
chloride, 1.6 mL (22.8 mmol) of DMSO, and 7.1 mL (50.9 mmol)
of Et3N affording aldehyde 5.4 (8.46 g, 91%) as a colorless oil:
6.3: [R]D -28.8 (c 1.03, CHCl3); IR (CCl4) 3447, 1705; 1H
NMR δ 1.16 (3 H, d, J ) 6.4 Hz), 1.31 (3 H, s), 1.33 (3 H, s),
1.43 (9 H, s), 1.45 (3 H, s), 1.49 (3 H, s), 2.60 (1 H, bs), 3.70-
3.75 (1 H, m), 3.89 (1H, d, J ) 5.4 Hz), 4.29 (1 H, dd, J ) 2.2,
4.9 Hz), 4.32 (1 H, dd, J ) 1.0, 8.1 Hz), 4.58 (1 H, dd, J ) 1.8,
7.8 Hz), 5.16 (1 H, d, J ) 9.2 Hz), 5.53 (1 H, d, J ) 5.0 Hz).
A solution of the above oxazolidine 6.2 (154 mg, 0.35 mmol)
and TsOH‚H2O (7 mg, 0.04 mmol) in MeOH (2 mL) was stirred
for 8 h, neutralized with Et3N, and then concentrated under
reduced pressure. Purification by flash chromatography on
silica gel (3:2 Et2O-hexanes) gave additional diacetonide 6.3
(112 mg, 80%).
1
[R]D +21.0 (c 1.03, CHCl3); IR 1694; H NMR (DMSO-d6, 85
°C): 1.25 (3 H, d, J ) 6.0 Hz), 1.35 (9 H, s), 1.50 (3 H, s), 1.55
(3 H, s), 3.80-4.06 (2 H, m), 6.16 (1 H, ddd, J ) 0.8, 7.7, 15.6
Hz), 6.88 (1 H, dd, J ) 7.5, 15.6 Hz), 9.59 (1 H, d, J ) 7.5 Hz).
Anal. Calcd for C14H23NO4: C; 62.43, H; 8.61, N; 5.20.
Found: C; 62.29, H; 8.67, N; 5.10.
(4S ,5S )-3-(t er t -B u t o x y c a r b o n y l)-2,2-d i m e t h y l-4-
[(1E,5E,3S,4S)-4-[ter t-bu tyld im eth ylsilyl)oxy]-3-h yd r oxy-
1,5-h ep ta d ien yl]-5-m eth yloxa zolid in e (5.5). The proce-
dure described above for alcohol 2.9 was employed with 557
mg (2.07 mmol) of aldehyde 5.4, 1.28 g (2.69 mmol) of (R)-
stannane 2.8, and 0.33 mL (2.68 mmol) of BF3‚OEt2 affording
alcohol 5.5 (772 mg, 82%) as a colorless oil: [R]D -0.3 (c 1.18,
Ester 6.4. To a suspension of alcohol 6.2 (108 mg, 0.27
mmol), Ph3P (105 mg, 0.40 mmol), and p-nitrobenzoic acid (68
mg, 0.40 mmol) in benzene (2 mL) was added 0.06 mL (0.04
mmol) of DEAD. After 48 h, the reaction mixture was
concentrated under reduced pressure. The residue was dis-
solved in Et2O (0.3 mL) and after 30 min, 0.15 mL of hexanes
was added. The resulting precipitate was filtered on Celite
and washed with a 1:1 mixture of hexanes-Et2O (1.4 mL). The
filtrate was concentrated under reduced pressure and the
residue was purified by flash chromatography on silica gel
(first column: 1:1, hexanes-Et2O, second column: 3:2, hex-
anes-EtOAc) affording 101 mg (74%) of a glassy solid: mp
86-88 °C; [R]D -50.3 (c 0.93, CHCl3); IR 3254, 3137, 1725,
1699, 1530, 1373; 1H NMR δ 1.31 (3 H, s), 1.33 (3 H, s), 1.38-
1.44 (15 H, m), 1.48 (3 H, s), 3.60-3.85 (2 H, m), 4.30-4.50 (3
H, m), 4.58 (1 H, dd, J ) 2.3, 7.9 Hz), 5.26 (1 H, bd, J ) 8.1
Hz), 5.44 (1 H, dq, J ) 5.8, 6.0 Hz), 5.54 (1 H, d, J ) 5.2 Hz),
8.18-8.25 (4 H, m). Anal. Calcd for C26H36N2O11: C; 56.56,
H; 8.24, N; 3.47. Found: C; 56.32, H; 8.08, N; 3.47.
6-[(ter t-Bu toxyca r bon yl)a m in o]-6,8-d id eoxy-1,2:3,4-d i-
O-isop r op ylid en e-D-er yth r o-r-D-ga la cto-oct op yr a n ose
(6.5). A solution of ester 6.4 (91 mg, 0.16 mmol) and KCN (6
mg, 0.08 mmol) in MeOH (1 mL) was stirred for 20 h and then
concentrated under reduced pressure. Purification by flash
chromatography on silica gel (3:2, hexanes-EtOAc) gave
alcohol 6.5 (59 mg, 89%) as a white solid: mp 48-50 °C; [R]D
-41.0 (c 0.80, CHCl3); IR 3431, 1703;1H NMR δ 1.24 (3 H, d,
J ) 6.7 Hz), 1.32 (3 H, s), 1.34 (3 H, s), 1.43 (9 H, s), 1.48 (3
H, s), 1.52 (3 H, s), 2.82 (1 H, bs), 3.75-3.83 (1 H, m), 4.02 (2
H, bs), 4.29 (1 H, dd, J ) 2.3, 5.0 Hz), 4.39 (1 H, dd, J ) 1.2,
7.9 Hz), 4.60 (1 H, dd, J ) 2.5, 8.0 Hz), 5.22 (1 H, bs), 5.53 (1
H, d, J ) 5.0 Hz).
1
CHCl3); IR 3459, 1700; H NMR (400 MHz), δ 0.01 (3 H, s),
0.04 (3 H, s), 0.87 (9 H, s), 1.22 (3 H, d, J ) 5.8 Hz), 1.41 (9 H,
s), 1.48 (3 H, s), 1.57 (3 H, s), 1.66 (3 H, dd, J ) 1.4, 6.5 Hz),
2.69 (1 H, bs), 3.65-3.85 (4 H, m), 5.30-5.70 (4 H, m). Anal.
Calcd for C24H45NO5Si: C; 63.26, H; 9.95, N; 3.07. Found: C;
63.18, H; 10.03, N; 2.99.
(4S ,5S )-3-(t er t -B u t o x y c a r b o n y l)-2,2-d i m e t h y l-4-
[(1E,5E,3S,4S)-3,4-bis-[(ter t-bu tyld im eth ylsilyl)oxy]-1,5-
h ep ta d ien yl]-5-m eth yloxa zolid in e (5.6). The procedure
described above for disilyl ether 2.10 was employed with 780
mg (1.71 mmol) of alcohol 5.5, 0.44 mL (3.78 mmol) of 2,6-
lutidine, and 0.69 mL (3.00 mmol) of TBSOTf affording disilyl
ether 5.6 (911 mg, 94%) as a colorless oil: [R]D -8.9 (c 1.05,
CHCl3); IR 1704; 1H NMR (400 MHz) δ -0.01 (3 H, s), 0.01 (3
H, s), 0.02 (3 H, s), 0.04 (3 H, s), 0.86 (9 H, s), 0.87 (9 H, s),
1.24 (3 H, d, J ) 5.8 Hz), 1.41 (12 H, s), 1.46 (3 H, s), 1.64 (3
H, d J ) 6.2 Hz), 3.75-3.79 (2 H, m), 3.95-4.05 (2 H, bs),
5.41-5.60 (4 H, m). Anal. Calcd for C30H59NO5Si2: C; 63.22,
H; 10.43, N; 2.46. Found: C; 63.27, H; 10.49, N; 2.39.
(4S ,5S )-3-(t er t -B u t o x y c a r b o n y l)-2,2-d i m e t h y l-4-
[(1R,2S,3S,4S,5S,6R)-3,4-b is-[(ter t-b u t yld im et h ylsilyl)-
oxy]-1,2,5,6-t et r a h yd r oxylh ep t yl]-5-m et h yloxa zolid in e
(5.7). The procedure described above for tetrol 3.1 was
employed with 570 mg (0.96 mmol) of diene 5.6, 565 mg (4.80
mmol) of NMO, and 2.0 mL (0.20 mmol) of 0.1 M OsO4 in H2O
affording tetrol 5.7 (446 mg, 73%) as a white glassy solid after
chromatography along with a mixture of isomers (104 mg,
17%): mp 54-56 °C; [R]D -6.02 (c 1.03, CHCl3); IR 3452, 1663;
1H NMR (400 MHz) δ 0.13 (3 H, s), 0.15 (3 H, s), 0.16 (6 H, s),
0.88 (18 H, s), 1.22 (3 H, d, J ) 6.5 Hz), 1.32 (3H, d, J ) 6.4
Hz), 1.44 (3 H, s), 1.47 (9 H, s), 1.61 (3 H, s), 2.12 (1 H, bd, J
) 9.8 Hz), 3.56 (1 H, bs), 3.64 (1 H, t, J ) 8.5 Hz), 3.71 (1 H,
d, J ) 8.2 Hz), 3.76 (1 H, dd, J ) 2.6, 6.8 Hz), 3.79-3.98 (4 H,
m), 4.10 (1 H, bs), 4.27 (1 H, bs), 4.37 (1 H, bd, J ) 5.4 Hz).
Anal. Calcd for C30H63NO9Si2: C; 56.42, H; 9.95, N; 2.20.
Found: C; 56.46, H; 9.98, N; 2.22.
6-Aceta m id o-6,8-d id eoxy-1,2:3,4-d i-O-isop r op ylid en e-
D-er yth r o-r-D-ga la cto-octop yr a n ose (6.7). A solution of the
N-BOC pyranoside 6.5 (11 mg, 0.03 mmol) in CH2Cl2-TFA
(1:1, 0.4 mL) was stirred at rt for 10 min, diluted with CH2-
Cl2, and then made basic with 5% NaOH. The aqueous layer
was extracted with CH2Cl2, and the combined extracts were
dried over Na2SO4 to give the crude amine 6.6 (7 mg, 82%):
1H NMR δ 1.15 (3 H, d, J ) 6.6 Hz), 1.31 (3 H, s), 1.34 (3 H,
Silyla ted La ctol 5.8. The procedure described above for
lactol 3.2 was employed with 606 mg (0.95 mmol) of tetrol 5.7

586 J . Org. Chem., Vol. 61, No. 2, 1996
Marshall and Beaudoin
s), 1.44 (3 H, s), 1.51 (3 H, s), 1.88 (3 H, s), 3.10 (1 H, dd, J )
4.6, 9.2 Hz), 3.54 (1 H, dd, J ) 1.7, 9.4 Hz), 4.00 (1 H, qd, J )
5.0, 6.2 Hz), 4.31 (1 H, dd, J ) 2.5, 5.2 Hz), 4.61 (1 H, dd, J )
2.5, 7.9 Hz), 5.50 (1 H, d, J ) 5.0 Hz).
1.99 (3 H, s), 3.03 (1 H, bs), 3.98-4.16 (3 H, m), 4.30 (1 H, dd,
J ) 2.2, 5.0 Hz), 4.44 (1 H, d, J ) 8.1 Hz), 4.61 (1 H, dd, J )
2.2, 7.9 Hz), 5.52 (1 H, d, J ) 5.0 Hz), 6.48 (1 H, d, J ) 6.6
Hz).
This material in MeOH (0.5 mL) was stirred with 3 drops
of Ac2O. After 15 h, the reaction mixture was quenched with
pyridine (4 drops) and then concentrated under reduced
pressure. The residue was dissolved in CH2Cl2, washed with
10% HCl and saturated NaHCO3, and dried over Na2SO4.
Purification by flash chromatography on silica gel (95:5
EtOAc-MeOH) gave acetamide 6.3 (7 mg, 94%) as a white
solid: mp 164-165 °C ([lit. mp 165.5-166.512c]; [R]D -54.0 (c
0.70, CHCl3) [lit. -53.8 (c 3.2, CHCl3)12c mp 166-167 °C, [R]D
-53.0 (c 0.98, CHCl3)12e] after recrystallization from EtOAc-
Ack n ow led gm en t. This research was supported by
Grant ROI AI31422 from the NIH Institute of Allergy
and Infectious Diseases.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
all intermediates (28 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
1
hexanes; IR 3400-3100, 1657 ; H NMR δ 1.24 (3 H, d, J )
6.3 Hz), 1.32 (3 H, s), 1.35 (3 H, s), 1.49 (3 H, s), 1.51 (3 H, s),
J O9517914