Synthesis and oxidation of N-aminoglyconolactams: A synthesis of mannostatin A

Article abstract of DOI:10.1002/hlca.200490217

The N-amino-ribono-1,5-lactam 4 was prepared in two high-yielding steps from the known methanesulfonate 2. Oxidation of 4 with t-BuOCl in the presence of 2,6-lutidine afforded the tetrazene 6 (63%). Oxidation with MnO₂ gave the deaminated lactam 7 (40%), which was also obtained, together with the lactone 8, upon oxidation of 4 with PhSeO₂H. Oxidation with Mn(OAc)₃/Cu(OAc)₂ provided the lactam 7 as the major and the dimer 9 as the minor product. Oxidation of 4 with 3 equiv. of Pb(OAc)4 in toluene at room temperature gave two cyclopentanes, viz. the acetoxy epoxide 10 and the diazo ketone 11 in a combined yield of 78%. Oxidation with Pb(OBz) ₄ provided 11 and the crystalline benzoyloxy epoxide 12. The crystal structure of 12 was established by X-ray analysis. The N-amino-glyconolactams 41, 46, and 51 were prepared similarly to 4. Their oxidation with Pb(OAc)4 provided the diazo ketones 56, 57, and 58 as the only isolable products. Oxidation of the N-amino-mannono-1,5-lactam 55 with Pb(OAc)₄ in the presence of DMSO gave the sulfoximine 59. Mannostatin A, a strong α-mannosidase inhibitor, was synthesized from the acetoxy epoxide 10 (obtained in 48% from 4) in seven steps and in an overall yield of 45%.

Full text of DOI:10.1002/hlca.200490217

Helvetica Chimica Acta Vol. 87 (2004)
2405
Synthesis and Oxidation of N-Aminoglyconolactams:
A Synthesis of Mannostatin A
by Guixian Hu and Andrea Vasella*
Laboratorium f¸r Organische Chemie, ETH-Hˆnggerberg, HCI, CH-8093Z¸rich
The N-amino-ribono-1,5-lactam 4 was prepared in two high-yielding steps from the known methanesul-
fonate 2. Oxidation of 4 with t-BuOCl in the presence of 2,6-lutidine afforded the tetrazene 6 (63%). Oxidation
with MnO2 gave the deaminated lactam 7 (40%), which was also obtained, together with the lactone 8, upon
oxidation of 4 with PhSeO2H. Oxidation with Mn(OAc)3/Cu(OAc)2 provided the lactam 7 as the major and the
dimer 9 as the minor product. Oxidation of 4 with 3equiv. of Pb(OAc) 4 in toluene at room temperature gave two
cyclopentanes, viz. the acetoxy epoxide 10 and the diazo ketone 11 in a combined yield of 78%. Oxidation with
Pb(OBz)4 provided 11 and the crystalline benzoyloxy epoxide 12. The crystal structure of 12 was established by
X-ray analysis. The N-amino-glyconolactams 41, 46, and 51 were prepared similarly to 4. Their oxidation with
Pb(OAc)4 provided the diazo ketones 56, 57, and 58 as the only isolable products. Oxidation of the N-amino-
mannono-1,5-lactam 55 with Pb(OAc)4 in the presence of DMSO gave the sulfoximine 59. Mannostatin A, a
strong a-mannosidase inhibitor, was synthesized from the acetoxy epoxide 10 (obtained in 48% from 4) in seven
steps and in an overall yield of 45%.
Introduction. Several naturally occurring cyclopentane derivatives1) are notable
glycosidase inhibitors2), such as trehazoline [3], allosamidine [4], and the mannosta-
tins [5 7]. Further cyclopentane-derived glycosidase inhibitors were prepared by Farr
et al. [8], J‰ger and co-workers [9][10], Lundt and co-workers [11], Ganem and co-
workers [12], Mehta and Mohal [13], and Reymond and co-workers [14 16]. We
synthesized and tested two bicyclo[3.1.0]hexanes (−cyclopropanated cyclopentanes×) in
the context of a comparison of the mechanism of action of snail b-mannosidase with the
one of the b-glucosidases from C. saccharolyticum and from sweet almonds [17]. This
synthesis renewed our interest in the transformation of carbohydrates into cyclo-
pentanes. Carbohydrates indeed appear to be ideal starting materials for the synthesis
of highly functionalized, enantiomerically pure cyclopentanes. The first general method
for the transformation of monosaccharides to cyclopentanes is based on a fragmenta-
tion and intramolecular 1,3-dipolar cycloaddition [18]. Intramolecular 1,3-dipolar
cycloadditions of oximes [19], nitrile oxides [9][20], and azomethine imines [21] have
also been widely exploited for the synthesis of functionalized cyclopentanes [8]. Other
methods for the transformation of carbohydrates into cyclopentanes3) are based on
free radical cyclizations4) of alkenes [11][25], aldehydes [26], hydrazones [27], and
oxime ethers [16][28], on carbanion cyclizations [14][29][30], tandem aldol-Wittig-
1
)
)
)
)
For reviews of carbapentoses and carbocyclic nucleosides, see [1].
For a review of aminocyclopentanes as glycosidase inhibitors, see [2].
For reviews, see [22][23].
2
3
4
For reviews, see [24].
¹ 2004 Verlag Helvetica Chimica Acta AG, Z¸rich

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Helvetica Chimica Acta Vol. 87 (2004)
type reactions [31], DielsÀAlder cycloadditions [32], [2 ‡ 2] photocycloaddition [33],
ring closing metathesis [34], rearrangements [23][35] including a ring contraction [36],
on the PausonÀKhand reaction [37], and the RambergÀB‰cklund rearrangement
[38].
We desired to combine the invention of a new method for the transformation of
monosaccharides into cyclopentanes with a synthesis of mannostatin A (1), a strong
competitive inhibitor of a-mannosidase from rat epididymis (Ki ˆ 4.8  10À8 M) [5].
Mannostatin A was isolated in 1989 by Aoyagi et al. [5 7], together with mannostatin
B (the corresponding (R)-sulfoxide), from the culture broth of Streptoverticillium
verticillus var. quantum. Mannostatin A has been synthesized a number of times
[30][39 45], but only once from carbohydrates [30][44], and once from myo-inositol
[41][42].
In devising a new method for the transformation of carbohydrates into cyclo-
pentanes, we noticed that the chemistry of N-aminoglyconolactams remained unex-
plored; such N-amino lactams were mentioned once only [46], whilst the chemistry of
non-carbohydrate-derived N-amino lactams has been studied5). Although not
precedented by these studies, oxidation of N-aminoglyconoloactams may lead to N-
acyldiazenes [50][51][53] and hence, by homo- or heterolytic bond cleavage and
extrusion of dinitrogen [51][54] to cyclopentane derivatives [55] (Scheme 1). A related
transformation is illustrated by the oxidation with MnO2 of cis-2-aminodihydro-1,3-
diphenylisoindole (a N,N-disubstituted hydrazine) to yield 27% of cis-1,2-diphenyl-
benzocyclobutene [56]. A protected N-amino lactam 4, ideally derived from the known
ribonolactone derivative 2, appeared a suitable intermediate for the synthesis of
mannostatin A (1). We have recently communicated the successful implementation of
this oxidation6), resulting in a new synthesis of 1 [58], and now we wish to provide
experimental details and a full account on the oxidation of different N-amino-
glyconolactams leading to cyclopentanes.
Scheme 1
5
)
)
For leading references, see [47 52].
Based on the diploma work of M. Zimmermann [57], supervised by Dr. C. V. Ramana.
6

Helvetica Chimica Acta Vol. 87 (2004)
2407
Results and Discussion. 1. Synthesis and Oxidation of the N-Amino-ribonolactam
4. Treatment of the known methanesulfonate 2 [59] with neat NH2NH2 ¥ H2O at room
temperature led to the N-amino-ribonolactam 3 as the only product (Scheme 2); it was
isolated by removing excess NH2NH2 ¥ H2O and hydrazinium methanesulfonate, and
silylated to yield 85% of the (tert-butyl)dimethylsilyl (TBS) ether 4. Deprotection of 3
provided 5 in a yield of 89%.
Scheme 2
a) NH2NH2 ¥ H2O, 238. b) TBSOTf, pyridine, CH2Cl2, 08; 85% from 2. c) THF/2n HCl 3:1, 80 8, 6 h; 89%.
The concept of the intended cyclopentane synthesis was tested by oxidizing the N-
amino-ribonolactam 4 (Scheme 3). t-BuOCl provided the tetrazene 6 (63%) instead of
the expected 1,2-diacyl-diazene [50] or of a cyclopentane derivative. It is known
that tetrazenes are formed upon oxidation of hydrazines7) with PhSeO2H [61],
KBrO3 ¥ HCl [62], KMnO4 [63], Br2 [64], MnO2 [60], and other oxidants [55][65].
Tetrazenes are considered to result from the dimerization of diazenes (N-amino-
nitrenes); 6 may, however, result from dimerization of an intermediate N-chlorohy-
drazide (X-philic substitution followed by elimination). When 4 was oxidized by t-
BuOCl in the presence of DMSO to trap the expected diazene, the yield of 6 dropped
to 12% and the lactam 7 resulting from deamination of 4 was isolated in a yield of 47%;
no sulfoximine or cyclopentane was observed. The formation of deamination products
upon oxidation of 1,2-disubstitued hydrazines is well precedented [63 65].
Oxidation of 4 with MnO2 gave the lactam 7 (40%) as the sole product (Scheme 3),
and oxidation with PhSeO2H in MeOH also afforded 7 (33%), together with the
lactone 8 (22%; Scheme 3).
We next investigated the oxidation of 4 by Mn(OAc)3 and Cu(OAc)2 in MeOH at
room temperature (Scheme 3). This oxidation gave 7 and the 1,2-diacylhydrazine 9 in
55 and 22% yield, respectively. The tetrazene 6 was not affected by these reaction
conditions, and can be excluded as intermediate. The product 7 could, however, be
formed via a tetrazane by elimination of a lactam anion. The simultaneously formed N-
acyltriazenium cation may be deprotonated and oxidized; substitution at the N-atom of
the ensuing N-acylated azide may lead to the diacylhydrazine 9.
7
)
For leading references to the oxidation of N-containing compounds by metal compounds, see [49][60].

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 3
a) t-BuOCl, 2,6-lutidine, THF, À 788, 1 h, then 238, 12 h; 63 % of 6. b) t-BuOCl, 2,6-lutidine, DMSO, THF,
À 788, 0.5 h, then 238, 2 h; 47% of 7, 12% of 6. c) MnO2, CH2Cl2, 238, 24 h; 40% of 7, 11% of 4. d) PhSeO2H,
MeOH, 238, 48 h; 3 3 % of7, 22% of 8. e) Mn(OAc)3 ¥ 2 H2O, Cu(OAc)2 ¥ H2O, MeOH, 238, 24 h; 55% of 7,
22% of 9. f) Pb(OAc)4, for conditions and yields, see Table 1. g) Pb(OBz)4, CH2Cl2, 238, 1 h; 23% of 12, 15% of
11. h) Pb(OBz)4, toluene, 238, 2 h; 33% of 12, 44% of 11.

Helvetica Chimica Acta Vol. 87 (2004)
2409
8
However, treatment of 4 with Pb(OAc)4 ) in CH2Cl2 gave a mixture of two
cyclopentanes, the acetoxy epoxide 10 and the diazo ketone 11, in a combined yield of
55% (Scheme 3). We cursorily examined9) the influence of the amount and the quality
of Pb(OAc)4 on the oxidation of 4. The relative amount of Pb(OAc)4 had no effect on
the ratio 10/11 (1.8 :1). Two equiv. of unpurified, commercial Pb(OAc)4 were required
to effect complete consumption of 4 within 1h at 23to 25 8. As shown in Table 1
(Entries 1 and 5), the quality of Pb(OAc)4 influenced the result to a limited extent only.
Three equivalents of commercial Pb(OAc)4 were used to investigate the influence of
the nature of the solvent and of the temperature. As shown in Table 1, the result of the
oxidation depends upon the nature of the solvent, with benzene and toluene giving the
best yields, reaching 47 49% of 10 and 26 30% of 11. Increasing the temperature did
not have a major influence on the yield of the acetoxy epoxide 10, but lowered the yield
the diazo ketone 11 (17% when the oxidation was performed at 1108; Entry 11)
evidencing that the diazo ketone 11 and/or a crucial intermediate are not stable at
higher temperatures. Oxidation on a gram scale (Entry 12) led to slightly improved
yields. An attempt to intercept a diazene by performing the oxidation in the presence of
DMSO yielded 25% of 10 and 28% of 11 besides 5% of the lactone 8; no other
products were observed.
Table 1. Oxidation of the N-Aminolactam 4 with Pb(OAc)4
4
Pb(OAc)4
Solvent
([ml])
Temp.
Time
[h]
3
Yield [%]a)
Entry
[mg] ([mmol])
[g] ([mmol])
[8]
10
11
1
2
3
4
5
6
7
8
9
105 (0.33)
316 (1.0)
316 (1.0)
316 (1.0)
316 (1.0)
316 (1.0)
316 (1.0)
316 (1.0)
316 (1.0)
316 (1.0)
316 (1.0)
3160 (10)
0.443 (1.0)b)
1.33 (3.0)b)
1.33 (3.0)
1.33 (3.0)
1.33 (3.0)
1.33 (3.0)
1.33 (3.0)
1.33 (3.0)
1.33 (3.0)
1.33 (3.0)
1.33 (3.0)
11.1 (25)
CH2Cl2 (4)
231.52.5
231 3 21
21
CH2Cl2 (40)
CH2Cl2 (30)
CH2Cl2 (30)
CH2Cl2 (30)
hexane (30)
cyclohexane (30)
benzene (30)
toluene (30)
toluene (30)
toluene (30)
toluene (250)
3
À 78
2
2
2
12
2
2
2
2
2
2
2321.5
30
28
0
23
22
23
23
23
23
23
70
110
23
32
38
13.5
18
48
26
47.5
48
26
27
10
11
12
45
17
48.5
29.5
a) Isolated yield. b) Purified by washing with Et2O and drying in vacuo.
As expected, oxidation of 4 with Pb(OBz)4 in CH2Cl2 provided the (crystalline)
benzoyloxy epoxide 12 and the diazo ketone 11, albeit in lower yields (12: 23 %;11:
15%; Scheme 3). The yield of 12 and 11 was increased to 33 and 42%, respectively, by
replacing CH2Cl2 with toluene.
8
)
)
For leading references to the oxidation of N-containing compounds by Pb(OAc)4 see [66 68].
A soln. of Pb(OAc)4 (1, 1.5, 2, 2.5, and 3equiv.) in CH 2Cl2 (4 ml) was treated with a soln. of 4 (100 mg,
0.32 mmol, 1 equiv.) in CH2Cl2 (2 ml) at r.t. After 60 min, the mixture was worked up and analysed by
1H-NMR to assess the ratio of starting material and products by integrating the HÀC(5) signal of 4 and of
the acetoxy phenoxide 10, and the HÀC(4) signal of the diazo ketone 11.
9

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Helvetica Chimica Acta Vol. 87 (2004)
The N-amino-ribonolactam 4 is characterized by a broad, D2O-exchangeable s of
two H at 4.46 ppm (exocyclic NH2). The N-acyl moiety is evidenced by a 13C s at
166.38 ppm, and six-membered N-aminolactam by a strong IR band at 1654 cmÀ1. The
structure of 3 and 4 was confirmed by X-ray analysis of the triol 510) (Fig. 1). The
4
deprotected N-aminolactam 5 adopts a H3 conformation in the solid state, which
agrees well with the NMR data (D2O solution). The NH2 group is located in the mean
plane of the lactam ring with one NH forming a H-bond to the carbonyl O-atom.
Fig. 1. Crystal structure of the N-amino-ribonolactam 5
1
The H- and 13C-NMR data of the lactam 7 could not be distinguished from those
reported for its enantiomer [69]; the specific rotation of 7 is very similar, and of
opposite sign. There is a single CˆO band in the IR spectra of the N-amino lactam 4
(1654), the lactam 7 (1681), the tetrazene 6 (1693), and the lactone 8 (1757); two bands
(1675 and 1701 cmÀ1) are found in N,N'-diacylhydrazine 9. There are no NH bands in
the IR spectra of 6, 8, and 9. The NMR spectra of 6 and 9 show J(2,3), J(3,4), J(4,5),
and J(4,5') values similar to those of 4 and 7 (see Table 2 in Exper. Part), and the NMR
data of 4, 6, 7, and 9 reveal a 2,3-O-isopropylidene-4-O-silyl-1,5-ribonolactam
‡
‡
substructure. The MALDI mass spectra show [M ‡ Na] and [M ‡ H] peaks of 7 at
m/z 324 and 302, respectively, corresponding peaks of 6 at m/z 651 and 623, and of 9 at
m/z 623and 601, suggesting that 6 and 9 are N-aminoribonolactam-derived dimers. The
tetrazene and bislactamyl structure was confirmed by elemental analysis. The crystal
structure of 610), co-crystallizing with two molecules of cyclohexane, was established by
a low-temperature X-ray analysis (Scheme 3 and Fig. 2). The conformation of both
ribonolactam rings of 6 is B1,4 , in agreement with a J(2,3) value of 7.2 Hz that is also
observed for 3, 4, and 7 9. The two CˆO groups and the four N-atoms are in the same
plane. Compared to the parent tetrazene N4H4, the bond lengths for NˆN and NÀN in
6 change from 1.205 and 1.429 ä in N4H4 [70] to 1.258 and 1.381/1.375 ä, respectively, in
agreement with values of other tetrazenes [71]. The NÀN bonds are also shorter than
those in the N-aminoribonolactam 5 (1.429 ä). The CˆO bond lengths of 6 (1.190/
1.199 ä) are in the normal range, and the NÀC(sp2) bond (1.392/1.389 ä) is shorter
than the NÀC(sp3) bond (1.473/1.477 ä).
10
)
The crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as
deposition No. CCDC-235432 (5), CCDC-235433 (6), CCDC-235434 (8), CCDC-235435 (12), CCDC-
202048 (29), CCDC-235436 (56), and CCDC-235437 (59). Copies of the data can be obtained, free of
charge, on application to the CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: ‡ 44(1223)336033; e-
mail: deposit@ccdc.cam.ac.uk).

Helvetica Chimica Acta Vol. 87 (2004)
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Fig. 2. Crystal structure of the ribono-tetrazene 6 ¥ 2 C6H12
The structure of the ribono-1,5-lactone 8 was originally reported for a compound
prepared by Saburi et al. [72], but the 1H- and 13C-NMR spectra of 8 differ from those
reported by these authors. Analysis of the original data suggested that the reported
compound, showing a typical 1,4-lactone IR band at 1776 cmÀ1, is the corresponding
ribono-1,4-lactone [73], evidenced by J(2,3) ˆ 5.6 Hz, and the absence of coupling
between HÀC(3) and HÀC(4). The NMR data of this 1,4-lactone agree indeed with
those reported by Saburi et al. [72]. The ribono-1,5-lactone structure of 8 is evidenced
by a strong IR band at 1757 cmÀ1, and its crystal structure was subsequently established
by X-ray analysis10) (Fig. 3).
Fig. 3. Crystal structure of the ribono-1,5-lactone 8
‡
The [M ‡ Na] peak at m/z 429.1703and the combustion analysis evidence the
elemental composition C21H30O6Si of the acetoxy epoxide 10. The two s at 1.49 and 1.36,
the s at 0.92, and the s at 0.12 ppm evidence that the 10 possesses the dimethyl-1,3-
dioxolanyl and the silyloxy moieties. A strong IR band at 1779 cmÀ1, a s at 2.15 ppm,

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Helvetica Chimica Acta Vol. 87 (2004)
and a 13C s at 169.43ppm evidence an activated AcO group, suggesting the structure of
an acetoxy epoxide. A dd at 5.01 ppm (J ˆ 5.3, 1.0 Hz) and the td at 4.41 ppm (J ꢀ 5.4,
1.0 Hz) were assigned to HÀC(2) and HÀC(3), respectively; a d (J ˆ 5.6 Hz)
resonating at 3.94 ppm was assigned to HÀC(4), geminal to the silyloxy group, and a t
at 3.74 ppm (J ˆ 1.0 Hz) to HÀC(5). A NOE (6.6%) between the dd at 5.01 and the td
at 4.41 ppm and a NOE (5.7%) between the td at 4.41 and the d at 3.94 ppm evidence
that HÀC(2), HÀC(3), and HÀC(4) are cis to each other, while a small NOE of 2.8%
between the d at 3.94 and the t at 3.74 ppm is agreement with the trans-orientation of
HÀC(4) and HÀC(5). The analogous benzoyloxy epoxide 12 shows similar NMR
spectra (see Table 3 in Exper. Part) except for the signals of the BzO group replacing
those of the AcO group. X-Ray analysis established the crystal structure of 1210)
(Fig. 4), and indirectly the one of 10. It shows the endo-orientation of the BzO group
relative to the dioxabicyclo[3.3.0]octane system, the exo-orientation of the epoxide O-
atom, and the proximity of the oxirane and the carbonyl O-atoms. The diazo ketone
substructure of 11 is evidenced by strong IR bands at 2102 and 1679 cmÀ1, and by a 13C s
at 191.06 ppm, and confirmed by a comparison of its NMR data with those of the lyxo-
configured diazo ketone 53 (see Table 3 in Exper. Part).
Fig. 4. Crystal structure of the benzoyloxy epoxide 12
A hypothetical reaction mechanism for the transformation of 4 into 10 and 11 is
formulated in Scheme 4. According to it, the N-aminolactam 4 is first acetoxylated to
the N'-acetoxy-N-amino lactam 13. Such acetoxylations are well precedented [52][74].
Elimination of the AcO group generates the diazenium cation 14 [75]. Alternatively,
substitution of an AcO ligand of Pb(OAc)4 by 4, followed by elimination of Pb(OAc)2
and AcOH, would also generate 14. Isomerization of 14 leads to the N-acyl-N-amino
immonium cation 15. This sequence is in keeping with the fruitless attempt to intercept
a nitrene (diazene) with DMSO and also with the results of AM1 calculations according
to which the cation 15 is more stable (in the gas phase) by 11.8 kcal/mol than the isomer
1411). (Formal) addition of acetate to 15 leads to the acetoxylated N-amino lactam 16.
A second N-acetoxylation/elimination (or substitution of AcOÀ of Pb(OAc)4, as
above) transforms 16 to 17, and further to 18 that reacts with AcOH (or acetate) to
form the anhydride 19. Most probably, heterolysis of the CÀOAc bond then generates
11
)
We thank Dr. Bruno Bernet for these calculations.

Helvetica Chimica Acta Vol. 87 (2004)
2413
the diazoanhydride 20 [67]. Intramolecular nucleophilic addition to the activated CˆO
group is hypothesized to lead to the two diastereoisomeric diazonium salts 21 and 22.
The configuration of the acetoxylated stereogenic C-atom results from the constraints
of the B¸rgiÀDunitz trajectory and of the reactive conformation of the a-alkoxy
carbonyl moiety (RO in p-plane of the CˆO group [76]). The conformation of the
second stereogenic C-atom results from the reacting conformers resulting from rotation
about the C(4)ÀC(5) bond of 20. The diastereoisomer 21, characterized by the trans-
orientation of the nucleophilic oxy and the leaving groups, will form the acetoxy
epoxide 10. The analogous cis-configurated 22 cannot undergo substitution; elimi-
nation of acetate and deprotonation will lead to the diazo ketone 11 [77]. Two
alternative pathways were considered. The azo compound 19 might be N-acylated to
generate 24 and, hence, the dihydro-oxadiazole 25 [78][79]. Such transformations were
well-studied for open-chain analogues [79][80], and the oxidation of acyclic N-
acylhydrazones with Pb(OAc)4 to D3-1,3,4-oxadiazolines has been reviewed several
times [67][68]. Loss of dinitrogen from 25 leads to the acetoxylated carbonyl ylide 26
[81]. A thermally allowed conrotatory electrocyclization of 26 can, however, be
excluded, as it would lead to a trans-oxirane [82]. Fragmentation of the carbonyl ylide
[83] to form a nucleophilic carbene 27 [84], followed by intramolecular nucleophilic
addition of the acetoxy carbene center to the CˆO group in 27, would also lead to the
acetoxy epoxide 10 [85]. This mechanism cannot be rigorously excluded. It should be
noted the endo-acetoxy epoxide 10 is more stable (in the gas phase) by 2.38 kcal/mol
than its diastereoisomer possessing an exo-oriented AcO group (AM1 calculations).
2. Synthesis of Mannostatin A. The synthesis started with the LiAlH4 reduction of
the acetoxy epoxide 10 to the trans-diol 28 (81%; Scheme 5). A H-bond between the
endo-oriented HOÀC(1) and OÀC(2), evidenced by a J(H,OH) value of 9.7 Hz,
should enhance the nucleophilicity of HOÀC(1) and favour a regioselective acylation.
Indeed, benzoylation of 28 by BzCl and TMEDA at À 408 gave a mixture of a
monobenzoate 30 (67%) and a dibenzoate 29 (26%). Crystal structure analysis (Fig. 5)
of the dibenzoate 2910) established the configuration of 29 and 28, and provided further
evidence for the structure of 10. Triflation of 28 at À 608 proceeded selectively to
provide the monotriflate 31 (91%) which was mesylated to yield 99% of 32. Treating 32
with excess NaSMe in THF gave the mesyloxy thioether 33 (95%). Substitution of the
MsO group by azide did not proceed at room temperature, and increasing the
temperature led to elimination. Desilylation of 33 at room temperature provided both
the alcohol 35 and the epoxide 34, while desilylation at À 308 yielded only the alcohol
35 (99%). Treating 35 with Cl3CCN in the presence of DBU led in high yields to the
trichloroacetimidate 36. Cyclization of isolated 36 in the presence of EtN(i-Pr)2
provided the dihydrooxazole 37 in a rather low yield, while treating the alcohol 35
sequentially with Cl3CCN, DBU, and EtN(i-Pr)2 yielded 80% of the desired
dihydrooxazole 37 besides 13% of the trichloroacetamide 36. The dihydrooxazole 37
was hydrolysed with HCl in MeOH to afford the hydrochloride of mannostatin A (1 ¥
HCl) [6]. Its 1H- and 13C-NMR spectra, and its specific rotation are in agreement with
published data [39][42][44][45]. Acetylation of 1 ¥ HCl provided the known tetraa-
cetate 38 [6]. Its melting point and its 1H- and 13C-NMR data are in agreement with the
literature [6][39][42][43], and its specific rotation corresponds to the highest
published value [42]. The free base 1 was obtained by ion-exchange chromatography

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 4. Hypothetical Reaction Mechanisms for the Transformation of 4 into the Acetoxy Epoxide 10 and the
Diazo Ketone 11
‡
of 1 ¥ HCl on Amberlite IR-120 (H ) resin with 0.5n aqueous NH3 as eluent; it inhibited
jack bean a-mannosidase with an IC50 of 48 nm ([7]: IC50 ˆ 70 nm).
For 28, two D2O exchangeable H (2.63and 2.46 ppm) and the broad IR band at
3540 cmÀ1 reveal two OH groups Their trans-configuration is evidenced by the HÀC(5)
td at 3.88 ppm (J ꢀ 9.0, 2.2 Hz) and the D2O exchangeable HOÀC(1) d at 2.63ppm

Helvetica Chimica Acta Vol. 87 (2004)
2415
Scheme 5
a) LiAlH4, THF, 08, 0.5 1 h; 81%. b) BzCl, TMEDA, CH2Cl2, À 408, 30 h; 26% of 29, 67% of 30. c) Tf2O,
pyridine, CH2Cl2, À 608, 3h; 91% of 31. d) Ms2O, pyridine, CH2Cl2, 08, 3h; 99%. e) NaSMe, 15-crown-5, THF,
238, 2 h; 95%. f) TBAF, THF, 08, 5 min; 30% of 34, 66% of 35. g) TBAF, THF, À 308, 2 h; 99% of 35. h)
Cl3CCN, DBU, CH2Cl2, 238, 1 h; 100% of 36. i) Cl3CCN, DBU, xylene, 238, 2 h, then EtN(i-Pr)2, 1108, 12 h;
13% of 36, 80% of 37. j) EtN(i-Pr)2, xylene, 1108, 24 h; 3 3 %.k) 7n HCl/MeOH 1:1, 238; 94 98%. l) Amberlite
‡
IR-120 (H ); 80%. m) Ac2O, pyridine; 93% from 37.
(J ˆ 9.7 Hz). The structure of the monobenzoate 30 is evidenced by the downfield shift
of the HÀC(1) dd (4.72 ppm), the downfield shift for the C(1) d (75.96 ppm), the
upfield shift for the C(2) d (74.23ppm) and the C(5) d (76.75 ppm). The monotri-
fluoroacetylation at O-C(1) of 28 leads to a downfield shift for HÀC(1) and C(1) of 31,
resonating at d 4.61 and 86.58 ppm, respectively. Mesylation to 32 is evidenced by a
downfield shift for HÀC(5) (5.14 ppm) and for C(5) at 83.53 ppm. The formation of
the thioether 33 is evidenced by a s at 3.08 ppm for the MsO group, a s at 2.23ppm
(MeS), a dd at 3.34 ppm for HÀC(1), and a d at 50.39 ppm for C(5). A d each at 3.58
and 3.62 ppm for 34 and two 13C d at 58.37 and at 61.59 ppm evidence the formation of
an oxirane ring. Formation of the imidate 36 is denoted by a strong IR absorption at
1669 cmÀ1, a broad s at 8.52 ppm, and a 13C s at 161.08 ppm. The dihydrooxazole 37 is
characterized by a strong IR band at 1653cm À1 and by the absence of NH and MsO
signals; the assignment of 1H-NMR signals is based on homonuclear irradiation
experiments (see Exper. Part).

2416
Helvetica Chimica Acta Vol. 87 (2004)
Fig. 5. Crystal structure of the dibenzoate 29
3. Synthesis and Oxidation of the N-Amino-d-lyxono-, -d-arabino-, -d-xylono-, and
-d-mannonolactams 41, 46, 51, and 55. We briefly tested the scope of the transformation
of N-amino lactams into cyclopentane derivatives by oxidizing the N-amino lactams 41,
46, 51, and 55 with Pb(OAc)4. These amino lactams were obtained from the lactones 39,
44, 49, and 53, respectively, by a similar route as described for the synthesis of 4. The D-
lyxonolactone 39 was prepared according to Pedersen and co-workers [59]. The
arabino- and xylonolactones 44 and 49 were synthesized from the known lactones 42
and 47 [86]. Regioselective mesitylenesulfonylation of 42 yielded 69% of the D-
arabinolactone 43; similarly, mesitylenesulfonylation of 47 resulted in 62% of the D-
xylonolactone 48 (Scheme 6). Methoxymethylation of 43 and 48 provided the desired
protected lactones 44 (86%) and 49 (78%). The D-mannonolactone 53 was prepared
by mesylating 52 [87].
Exposure of the lyxonolactone 39 to hydrazine hydrate gave the N-amino-lyxono-
1,5-lactam 40, which was protected as the TBS ether 41 (64% from 39). Similarly, 44
gave the N-aminopiperidinone 45 and the corresponding silyl ether 46 (81%). In the
same way, 49 was transformed into 50 and further into 51 (85%). However, treatment
of 53 with NH2NH2 ¥ H2O at 238 and then at 608, followed by silylation, gave the
crystalline N-aminopyrrolidinone 55 (92% from 53). The l-allo configuration of 54
and 55 evidences that hydrazinolysis of the lactones is accompanied by formation and
then regioselective opening of an epoxide. These transformations find a precedent in
the hydrazinolysis of ethyl 5-bromopentanoate that provided exclusively N-amino-
pentane-1,5-lactam [47] and in the ammonolysis of lactones possessing a suitably
located leaving group leading to lactams [88]. These results are consistent with the
hypothesis that excess ammonia or hydrazine promotes an intramolecular nucleophilic
attack by the N-center of the amide moiety, presumably by progressive deprotonation
of the acylamino group, while neutral, or acidic conditions promote a nucleophilic
attack by the O-center of the amide moiety [89]. In addition, the position of the amide/

Helvetica Chimica Acta Vol. 87 (2004)
2417
Scheme 6
a) NH2NH2 ¥ H2O, 238. b) TBSOTf, pyridine, CH2Cl2, 08; 64% of 41 from 39, 81% of 46 from 44, 85% of 51
from 49. c) MtsCl, pyridine, 0 238; 69% of 43, 62% of 48. d) CH2(OMe)2, P2O5, 238; 86% of 44, 78% of 49. e)
MsCl, pyridine, CH2Cl2, 0 238, 13h; 80%. f) NH2NH2 ¥ H2O, 238, 14h, 608, 3h; 97%. g) TBSOTf, pyridine,
CH2Cl2, 08, 1 h, 238, 24 h; 95%.
hydroxy imine equilibrium of N-acylhydrazines may be more strongly shifted towards
the imine form than the one of amides, considering that the pKHA of N-acylhydrazines
(dissociation of C(O)NH) is lower by ca. 2 pK units than the one of amides [90]; this
also would favour nucleophilic attack by N rather than by O.
Treatment of the amino lactam 41 in toluene with excess Pb(OAc)4 under the
conditions optimized for the oxidation of 4 provided the diazo ketone 56 (37%) as the
only conveniently isolated product (Scheme 7). Similarly, 46 and 51 provided only the
diazo ketones 57 (22%) and 58 (25%). Oxidation of the N-aminoallono-1,4-lactam 55,
however, led to generation of a purple colour that disappeared within a few minutes.
1
The H-NMR spectrum of the crude was in keeping with a mixture of two major
products that could not, however, be isolated by column chromatography. These
observations suggested the intermediate formation of a diazene. In keeping with this,
oxidation of 55 with Pb(OAc)4 in the presence of DMSO led to the crystalline

2418
Helvetica Chimica Acta Vol. 87 (2004)
sulfoximine 59 (54%). These results show the strong influence of the structure of the N-
amino lactams and of the reaction conditions on the course of the reaction. Further
studies are ongoing.
Scheme 7
a) Pb(OAc)4, toluene, 238, 1 h; 37% of 56, 22% of 57, 25% of 58. b) Pb(OAc)4, toluene, DMSO, 08, 2 h; 54%.
The N-amino lactams 41, 46, and 51 show a strong CˆO band at 1650 1660 cmÀ1, a
broad D2O exchangeable s (2 H) around 4.4 ppm, and a 13C s at ca. 166 168 ppm. A
strong IR band at 1718 cmÀ1, a broad D2O exchangeable s (2 H) at 3.94 ppm, and a 13C s
at 169.45 ppm suggest that 55 is a five-membered N-amino 1,4-lactam.
The l-allo configuration of 54 and 55 was deduced from a comparison of the small
J(3,4) ˆ 0 and J(4,5) ˆ 1.2 Hz with the corresponding J values of the D-manno-
configured 52 (J(3,4) ˆ 2.5, J(4,5) ˆ 8.1 Hz) and confirmed by transforming 55 into 59
whose crystal structure was established by X-ray analysis (see Fig. 7). The diazo ketone
moiety of 56 58 is evidenced by IR bands around 2100 cmÀ1 and three 13C s at 192.94,
192.00, and 190.93ppm, respectively. The structure of the diazo ketone 56 was
established by X-ray analysis10) (Fig. 6). The atoms of the diazo ketone subunit lie in
the same plane and the bond lengths (OˆCÀCˆNˆN: 1.224/1.425/1.316/1.130 ä)
agree well with those of [(benzyloxy)carbonyl]-3-diazopyrrolidin-2-one (1.222/1.437/
1.301/1.130 ä) [91], possessing a longer CˆO bond than that of a trimethyltin
diazoacetate ester (1.196/1.446/1.317/1.119 ä) [92]. The small coupling of 0.6 Hz
between a d at 5.23ppm and a dd at 4.43ppm in the 1H-NMR spectrum of 56 is in
agreement with the H(4)ÀC(4)ÀC(3)ÀH(3) torsion angle (q ꢀ 858) of the crystal
structure. Similarly, a HÀC(4) d was observed at 5.33 ppm for 11, at 5.28 ppm for 57,
and at 5.09 ppm for 58 (see Table 3 in Exper. Part). The constitution of the sulfoximine
59 is evidenced by the elemental analysis and by two s at 3.20 and 3.14 ppm and two 13
C
q at 40.83and 40.14 ppm, and the l-allo configuration is evidenced by a large J(2,3)
value of 6.2 Hz and by the HÀC(4) s at 3.98 ppm. The crystal structure of 59 was
established by X-ray analysis10) (Fig. 7), which also allows to assign the l-allono-
configuration to 55.

Helvetica Chimica Acta Vol. 87 (2004)
Fig. 6. Crystal structure of the diazo ketone 56
Fig. 7. Crystal structure of the sulfoximine 59
2419
We thank Dr. B. Schweizer for the crystal-structure determination, Dr. B. Bernet for checking the Exper.
Part, and the Swiss National Science Foundation and F. Hoffman-La Roche AG, Basel, for generous support.
Experimental Part
General. Unless specified otherwise, reactions were carried out under a N2 atmosphere. Solvents were
removed under reduced pressure (rotatory evaporator). CH2Cl2 was distilled over CaH2 and THF was distilled
over Na/benzophenone immediately before use. DMF was dried over 4-ä molecular sieves. Et3N was distilled
over CaH2 and stored over 4-ä molecular sieves. Organic phases were dried with MgSO4. TLC: Merck silica gel
60F-254 plates; detection with UV and/or by heating with −mostain× (400 ml of 10% H2SO4 soln., 20 g of
(NH4)6Mo7O24 ¥ 6 H2O, 0.4 g of Ce(SO4)2). Melting points are uncorrected. Optical rotations [a]2D5 were
determined at 589 nm. UV spectra were taken in a 1-cm cell at 258 in the range of 200 to 800 nm (log e values in
parenthesis). IR Spectra were recorded on a Perkin-Elmer 298 FT-IR spectrometer. NMR spectra were
recorded at 200 or 300 MHz apparatus using CDCl3 as the solvent. Crystal structures were analysed by the direct
method (SIR 97), and non-H-atoms were refined anisotropically with SHELX-97.
5-Deoxy-5-hydrazino-2,3-O-isopropylidene-d-ribono-1,5-lactam (3). A suspension of 2,3-O-isopropyli-
dene-5-O-(methylsulfonyl)-ribono-1,4-lactone (2) [59] (2.66 g, 10 mmol) in NH2NH2 ¥ H2O (4 ml) was stirred at
238 for 6 h. The resulting clear soln. was co-evaporated with toluene (2 Â 300 ml). A soln. of the residue in
CH2Cl2 (150 ml, formation of some crystals) was dried and evaporated to afford 3 (2.02 g, quant.). Colourless
oil. 1H-NMR (300 MHz, CDCl3): see Table 2; additionally, 4.48 (br. s, exchange with D2O, NH2); 2.75 2.35 (br.
s, HOÀC(4), exchange with D2O); 1.51, 1.42 (2s, Me2C). 13C-NMR (75 MHz, CDCl3): see Table 2; additionally,
‡
‡
111.10 (s, Me2C); 26.60, 24.87 (2q, Me2C). ESI-MS: 241 (23, [M ‡ K] ), 225 (100, [M ‡ Na] ), 203(4, [ M ‡
‡
H] ).

2420
Helvetica Chimica Acta Vol. 87 (2004)
Table 2. Selected 1H- and 13C-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] for the N-Amino-
ribonolactams and for the Oxidation Products of 4 in CDCl3
3
4
5a)
6
7
8
9
HÀC(2)
HÀC(3)
HÀC(4)
HÀC(5)
H'ÀC(5)
J(2,3)
4.59
4.53
4.10
3.73
3.59
7.9
4.47
4.39
4.12
3.76
3.41
5.9
4.29
4.65
4.48
4.22
4.09
3.89
7.2
4.42 4.34
4.42 4.34
4.09
4.57
4.48
4.17
4.35
4.09
8.4
4.54
4.26 4.21
4.26 4.21
3.65
4.47 4.36
4.47 4.36
3.75
3.52
3.54
3.13
3.43
b
3.1
)
6.5
b
b
J(3,4)
3.4
1.9
)
2.5
1.9
3.3
)
J(4,5)
J(4,5')
J(5,5')
7.5
3.4
12.8
9.36.4
4.3
11.8
7.8
9.0
6.38.4
10.6
11.4
3.1
13.4
4.4
11.8
1.8
4.0
11.4
11.2
3
4
5a)
6
7
8
9
C(1)
C(2)
C(3)
C(4)
C(5)
165.80
73.48
75.39
64.26
51.82
166.38
73.81
76.68
65.72
52.11
172.07
71.06
73.79
66.57
54.44
165.50
170.18
73.69
76.17
168.53
72.39
75.00
65.51
64.92
165.46
74.02
76.37
75.70c)
74.55c)
65.0366.46
46.24
67.86
42.79
50.26
a) In D2O. b) Not assigned. c) Assignments may be interchanged.
4-O-[(tert-Butyl)dimethylsilyl]-5-deoxy-5-hydrazino-2,3-O-isopropylidene-d-ribono-1,5-lactam (4). (tert-
Butyl)dimethylsilyl trifluromethanesulfonate (TBSOTf; 18 ml, 75 mmol) was added over 10 min to a soln. of 3
(10.1 g, 50 mmol) in CH2Cl2 (100 ml) and pyridine (30 ml) at 08. The mixture was stirred for 1 h at 08 and for 10 h
at 238, treated with H2O (100 ml), and extracted with CH2Cl2 (3 Â 150 ml). The combined org. phases were
dried and evaporated. FC (cyclohexane/AcOEt 1:1) and crystallization from hexane gave 4 (13.5 g, 85%).
White crystals. M.p. 105 105.58 (hexane). Rf (cyclohexane/AcOEt 1:2) 0.33. [a]2D5 ˆ À6.9 (c ˆ 0.61, CHCl3). IR
(CHCl3): 3321w, 3030w, 2956m, 2933m, 2899w, 2860m, 1654s, 1616m, 1472m, 1384m, 1376m, 1260s, 1231m,
1
1166m, 1134s, 1096m, 1088m, 1053w, 988w, 881s, 83 9s. H-NMR (300 MHz, CDCl3): see Table 2; additionally,
4.46 (s, exchanged with D2O, NH2); 4.39 (br. dd, J ꢀ 5.9, 1.9, addition of D2O and irrad. at 3.41 ! sharp dd, J ˆ
6.2, 2.5, HÀC(3)); 1.43, 1.39 (2s, Me2C); 0.90 (s, Me3C); 0.12, 0.11 (2s, Me2Si). 13C-NMR (75 MHz, CDCl3): see
Table 2, additionally, 111.22 (s, Me2C); 27.17, 25.57 (2q, Me2C); 26.00 (q, Me3C); 18.45 (s, Me3C); À 4.35, À 4.45
‡
‡
(2q, Me2Si). MALDI-MS: 339 (35, [M ‡ Na] ), 317 (75, [M ‡ H] ). Anal. calc. for C14H28N2O4Si (316.47): C
53.13, H 8.92, N 8.85; found: C 53.39, H 8.86, N 8.86.
5-Deoxy-5-hydrazino-d-ribono-1,5-lactam (5). A soln. of 3 (800 mg, 3.96 mmol) in THF/2N HCl 3:1
(30 ml) was boiled under reflux at 808 for 6 h, concentrated to 1/4 of its volume, and filtered through a small
column packed with Amberlite IRA-910 (HCOÀ3 form, elution with H2O). Lyophilization gave 5 (560 mg, 89%),
which was recrystallized in H2O/EtOH. Colourless crystals. M.p. 150 1518 (H2O/EtOH). [a]2D5 ˆ ‡59.5 (c ˆ 1.0,
H2O). pKa ˆ 6.91. IR (KBr): 3469s, 3319s, 3258s, 2911m, 2862s, 1628s, 1587s, 1510m, 1469m, 1413m, 1359m,
1327m, 1290m, 1272s, 1250m, 1227m, 1207m, 1152s, 1125m, 1109s, 1055s, 982m, 944s, 906w, 83 5m. 1H-NMR
(300 MHz, D2O): see Table 2, additionally, 4.26 4.21 (m, HÀC(3), HÀC(4)). 13C-NMR (75 MHz, D2O): see
‡
Table 2. EI-MS: 162 (100, M ). Anal. calc. for C5H10N2O4 (162.14): C 37.04, H 6.22, N 17.28; found: C 37.29, H
6.25, N 17.16.
Crystal Structure of 5. Recrystallization of 5 in H2O/MeOH/Et2O gave crystals suitable for X-ray analysis:
C5H10N2O4 (162.14); orthorhombic P212121; a ˆ 6.438 (6) ä, b ˆ 7.916 (4) ä, c ˆ 13.256 (6) ä, b ˆ 908; Vˆ 675.6
(8) ä3; Dcalc. ˆ 1.594 Mg/m3; Z ˆ 4. From a crystal of size 0.30  0.25  0.20 mm, 1156 reflections were measured
on an Enraf Nonius CAD-4 diffractometer with MoKa radiation (graphite monochromator, l ˆ 0.71073ä) at
170 (2) K. R ˆ 0.0371, Rw ˆ 0.0957. H-Atoms were obtained from a difference Fourier map and refined
isotropically.
Oxidation of 4-O-[(tert-Butyl)dimethylsilyl]-5-deoxy-5-hydrazino-2,3-O-isopropylidene-d-ribono-1,5-lac-
tam (4) with t-BuOCl. A soln. of 4 (270 mg, 0.85 mmol) and 2,6-lutidine (300 mg, 2.8 mmol) in THF (4 ml) was

Helvetica Chimica Acta Vol. 87 (2004)
2421
cooled to À 788, treated dropwise with t-butyl hypochlorite (t-BuOCl; 290 ml, 2.55 mmol), stirried for 1 h,
warmed to 238, stirred for 12 h, and filtered (Et2O). Evaporation and FC (hexane/AcOEt 1:2) gave 6 (168 mg,
63%). White crystals.
Data of Bis{5-amino-4-O-[(tert-butyl)dimethylsilyl]-5-deoxy-2,3-O-isopropylidene-d-ribono-1,5-lactam-
5a-yl}diazene (6). White crystals (cyclohexane/Et2O). M.p.: sintering at 117 1198 and melting at 156 1578
with slightly dec. Rf (cyclohexane/AcOEt 1:4) 0.45. [a]2D5 ˆ ‡69.4 (c ˆ 0.8, CHCl3). IR (CHCl3): 2994w, 2931m,
2859m, 1693s, 1464m, 1377s, 1321m, 1258s, 1156s, 1127m, 1101s, 1053w, 989m, 957m, 883m, 83 9s. 1H-NMR
(300 MHz, CDCl3): see Table 2; additionally, 1.48, 1.40 (2s, Me2C); 0.86 (s, Me3C); 0.09, 0.06 (2s, Me2Si).
13C-NMR (50 MHz, CDCl3): see Table 2; additionally, 111.66 (s, Me2C); 26.46, 24.93(2 q, Me2C); 25.66 (q,
‡
Me3C); 18.08 (s, Me3C); À 4.69, À 4.88 (2q, Me2Si). MALDI-MS: 651 (100, [M ‡ Na] ), 623(77, [ M À N2 ‡
‡
Na] ). Anal. calc. for C28H52N4O8Si2 (628.91): C 53.47, H 8.33, N 8.91; found: C 53.58, H 8.16, N 8.88.
Crystal Structure of 6 ¥ 2 (C6H12). Recrystallization of 6 in cyclohexane/benzene gave crystals suitable for
X-ray analysis: C28H52N4O8Si2 ¥ 2 (C6H12) (797.24); monoclinic P21; a ˆ 12.5480 (6) ä, b ˆ 14.8854 (8) ä, c ˆ
13.16631 (10) ä, b ˆ 99.641 (3)8; Vˆ 2424.5 (3) ä3; Dcalc. ˆ 1.092 Mg/m3; Z ˆ 2. From a crystal of size 0.56 Â
0.2 Â 0.1 mm, 7450 reflections were measured on an KappyCCD diffractometer with MoKa radiation (graphite
monochromator, l ˆ 0.71073ä) at 143K. R ˆ 0.1103, Rw ˆ 0.2613.
Oxidation of 4 with t-BuOCl in the Presence of DMSO. A soln. of 4 (64 mg, 0.2 mmol), 2,6-lutidine (82 mg,
0.7 mmol), and DMSO (0.2 ml) in THF (2 ml) was cooled to À 788, treated with t-BuOCl (68 ml, 0.6 mmol) for
0.5 h, warmed to 238, stirred for 2 h, and filtered (Et2O). Evaporation and FC (Et2O/MeOH 29 :1) gave 6 (7 mg,
12%) and 7 (28 mg, 47%).
Data of 5-Amino-4-O-[(tert-butyl)dimethylsilyl]-5-deoxy-2,3-O-isopropylidene-d-ribono-1,5-lactam (7).
M.p. 117.5 118.58 (hexane/Et2O). Rf (Et2O/MeOH 20 :1) 0.52. [a]2D4 ˆ 17.4 (c ˆ 0.7, CHCl3). IR (CHCl3): 3404w,
3216w, 3002w, 2956m, 2932m, 2898w, 2859m, 1681s, 1481w, 1472w, 1463w, 1384m, 1375m, 1258m, 1167m, 1132m,
1093m, 1085m, 1057m, 1006w, 985w, 93 4w, 881m, 862m, 83 8m. 1H-NMR (300 MHz, CDCl3): see Table 2;
additionally, 7.22 (br. s, NH); 1.48, 1.40 (2s, Me2C); 0.89 (s, Me3C); 0.11, 0.10 (2s, Me2Si). 13C-NMR (75 MHz,
CDCl3): see Table 2; additionally, 110.97 (s, Me2C); 26.97, 25.46 (2q, Me2C); 25.91 (q, Me3C); 18.37 (s, Me3C);
‡
‡
À 4.47, À 4.57 (2q, Me2Si). MALDI-MS: 324 (100, [M ‡ Na] ), 302 (80, [M ‡ H] ). Anal. calc. for C14H27NO4Si
(301.46): C 55.78, H 9.03, N 4.65; found: C 55.95, H 9.08, N 4.62.
Oxidation of 4 with MnO2 [93]. A soln. of 4 (158 mg, 0.5 mmol) in CH2Cl2 (5 ml) was added to a suspension
of MnO2 (435 mg, 0.5 mmol) in CH2Cl2 (5 ml). The mixture was heated to reflux for 24 h and filtered through
silica gel (AcOEt). Evaporation and FC (Et2O/MeOH 50 :1) gave 7 as white crystals (62 mg, 40%) and 5
(18 mg, 11%).
Oxidation of 4 with Phenylseleninic Acid (PhSeO2H). A cooled (08) soln. of 4 (96 mg, 0.3mmol) in MeOH
(2 ml) was treated with PhSeO2H (60 mg, 0.3mmol), stirred at 23 8 for 48 h, treated with sat. NaHCO3 soln., and
extracted with CH2Cl2. The org. layers were dried (MgSO4) and evaporated. FC (cyclohexane/AcOEt 4 :1 !
1:4) gave 8 (20 mg, 22%) and 7 (33 mg, 33%).
Data of 4-O-[(tert-Butyl)dimethylsilyl]-2,3-O-isopropylidene-d-ribono-1,5-lactone (8). White crystals.
M.p. 119 1208 (hexane/AcOEt). Rf (cyclohexane/AcOEt 2 :1) 0.41. [a]2D5 ˆ ‡6.5 (c ˆ 0.23, CHCl3). IR (neat):
2962w, 2930w, 2886w, 2853m, 1757s, 1474w, 1382m, 1376m, 1364w, 1258s, 1233m, 1186s, 1159s, 1100s, 1088s,
1070w, 1054s, 1008w, 984s, 973m, 950vs, 923w, 909m, 865s, 83 2s. 1H-NMR (300 MHz, CDCl3): see Table 2;
additionally, 1.53, 1.40 (2s, Me2C); 0.90 (s, Me3C); 0.116, 0.112 (2s, Me2Si). 13C-NMR (75 MHz, CDCl3): see
Table 2; additionally, 111.50 (s, Me2C); 26.14, 24.77 (2q, Me2C); 25.77 (q, Me3C); 18.31 (s, Me3C); À 4.39, À 4.86
‡
‡
‡
(2q, Me2Si). MALDI-MS: 325 (100, [M ‡ Na] ). HR-MALDI-MS: 325.1438 (100, [M ‡ Na] , C14H26O5NaSi ;
calc. 325.1442). Anal. calc. for C14H26O5Si (302.44): C 55.60, H 8.67; found: C 55.71, H 8.42.
Crystal Structure of 8. Recrystallization of 8 in hexane/AcOEt gave crystals suitable for X-ray analysis:
C14H26O5Si (302.44); orthorhombic P212121; a ˆ 8.6484 (3) ä, b ˆ 10.3483 (3) ä, c ˆ 19.5168 (7) ä, b ˆ 104.695
(2)8; Vˆ 1746.68 (10) ä3; Dcalc. ˆ 1.150 Mg/m3; Z ˆ 4. From a crystal of size 0.24  0.2  0.1 mm, 3989 reflections
were measured on an KappyCCD diffractometer with MoKa radiation (graphite monochromator, l ˆ 0.71073
ä) at 298 K. R ˆ 0.0701, Rw ˆ 0.1574.
Oxidation of 4 with Mn(OAc)3 and Cu(OAc)2. A soln. of 4 (95 mg, 0.3mmol) in MeOH (2 ml) was added
dropwise to a suspension of Mn(OAc)3 ¥ 2 H2O (846 mg, 3.0 mmol) and Cu(OAc)2 ¥ H2O (60 mg, 0.3mmol) in
MeOH (2 ml). The mixture was stirred at 238 for 24 h and filtered through silica gel (AcOEt). Evaporation and
FC (cyclohexane/AcOEt 1:1 ! 1 :2) gave 9 (20 mg, 22%) and 7 (50 mg, 55%).
Data of 5,5'-Bi{5-amino-4-O-[(tert-butyl)dimethylsilyl]-5-deoxy-2,3-O-isopropylidene-d-ribono-1,5-lac-
tam} (9). Rf (cyclohexane/AcOEt 1:2) 0.4. [a]D25 ˆ ‡3.4 (c ˆ 0.53, CHCl3). IR (CHCl3): 2992m, 2955m, 2932s,
2900m, 2859m, 1701s, 1675s, 1471m, 1414m, 1384m, 1376m, 1258s, 1164m, 1128s, 1094s, 1055m, 992m, 956w,

2422
Helvetica Chimica Acta Vol. 87 (2004)
936m, 882s, 83 9s. 1H-NMR (300 MHz, CDCl3): see Table 2; additionally, 1.49, 1.41 (2s, Me2C); 0.90 (s, Me3C);
0.14, 0.12 (2s, Me2Si). 13C-NMR (75 MHz, CDCl3): see Table 2; additionally, 111.27 (s, Me2C); 27.18, 25.21 (2q,
‡
Me2C); 26.12 (q, Me3C); 18.48 (s, Me3C); À 4.36, À 4.38 (2q, Me2Si). MALDI-MS: 623(100, [ M ‡ Na] ), 601
‡
(64, [M ‡ H] ). Anal. calc. for C28H52N2O8Si2 (600.94): C 55.97, H 8.72, N 4.66; found: C 55.96, H 8.59, N 4.71.
General Procedure for the Oxidation of 4 with Pb(OAc)4. At the temp. specified in Table 1, a soln. of 4 in
dry CH2Cl2, hexane, cyclohexane, benzene, or toluene was treated with a soln. of Pb(OAc)4 in the same solvent,
stirred for the indicated duration, treated with H2O, extracted with Et2O, and dried (MgSO4). Evaporation and
FC (cyclohexane/AcOEt 10 :1 ! 2.1) gave 10 and 11.
Data of 2D-(1,5/1,2,3,4)-1-O-Acetyl-1,5-anhydro-4-O-[(tert-butyl)dimethylsilyl]-2,3-O-isopropylidenecy-
clopentane-1,1,2,3,4,5-hexol (10). Colourless liquid. Rf (cyclohexane/AcOEt 4 :1) 0.67. [a]2D5 ˆ ‡27.4 (c ˆ 0.5,
CHCl3). IR (CHCl3): 3031w, 2952m, 2932m, 2858m, 1779s, 1472w, 1464w, 1438w, 1373m, 1251m, 1167m, 1136s,
1090s, 1018m, 973w, 866s, 83 9s. 1H-NMR (300 MHz, CDCl3): see Table 3, additionally, 4.41 (irrad. at 5.01 !
NOE of 6.6%, irrad. at 3.94 ! NOE of 5.7%, HÀC(3)); 3.94 (irrad. at 3.74 ! NOE of 2.8%, HÀC(4)); 3.74
(irrad. at 3.94 ! NOE of 2.8%, HÀC(5)); 2.15 (s, AcO); 1.49, 1.36 (2s, Me2C); 0.92 (s, Me3C); 0.12 (s, Me2Si).
13C-NMR (75 MHz, CDCl3): see Table 3; additionally, 169.43( s, CˆO); 113.71 (s, Me2C); 26.88 (q, Me2C); 26.12
‡
(q, Me3C); 21.19 (q, Me); 18.80 (s, Me3C); À 4.28, À 4.95 (2q, Me2Si). ESI-MS: 383 (14, [M ‡ K] ), 367 (19,
‡
‡
‡
[M ‡ Na] ), 362 (90, [M ‡ NH4] ), 345 (100, [M ‡ H] ). Anal. calc. for C16H28O6Si (344.48): C 55.79, H 8.19;
found: C 55.82, H 8.21.
1
Table 3. Chemical Shifts [ppm] and Coupling Constants [Hz] for the Cyclopentyl H- and 13C-NMR Signals of
the Acyloxy Epoxides 10 and 12, and of the Diazo Ketones 11, 56, 57, and 58 in CDCl3
10
5.01
4.41
3.94
3.74
5.3
5.6
0
12
5.16
4.49
4.00
3.88
5.3
5.6
0
11
4.49
4.62
5.33
56a)
5758
HÀC(2)
HÀC(3)
HÀC(4)
HÀC(5)
J(2,3)
4.74
4.43
5.23
4.534.16
4.07
5.28
4.07
5.09
5.6
5.3
5.6
0.6
8.7
5.0
6.5
4.0
J(3,4)
J(4,5)
J(2,5)
J(3,5)
1.0
1.0
0.6
1.0
10b)
12
11b)
56
5758
C(1)
C(2)
C(3)
C(4)
C(5)
86.78
78.05
81.44
69.65
64.28
87.37
78.28
81.74
69.92
64.46
191.06
81.31
76.34
68.87
192.94
82.54c)
80.43 c)
73.94
192.00
78.46c)
77.28c)
68.69
190.93
85.27c)
80.74c)
72.47
d
d
d
d
)
)
)
)
b
a) Coupling constants expected for the conformation in the solid state. ) Assignment based on a 1H,13C-COSY
spectrum. c) Assignments may be interchanged. d) Hidden.
Data of 2D-(2,3,4/0)-4-O-[(tert-Butyl)dimethylsilyl]-5-diazo-2,3-O-isopropylidene-2,3,4-trihydroxycyclo-
pentanone (11). Yellow crystals. M.p. 117 119.58 (hexane/Et2O). Rf (hexane/AcOEt 4 :1) 0.28. [a]2D5 ˆ ‡43.3
(c ˆ 0.51, CHCl3). UV (MeOH): 300 (3.23), 255 (3.89). IR (CHCl3): 3019m, 2954w, 2932w, 2860w, 2102s, 1679s,
1472w, 1384w, 1375m, 1349m, 1326m, 1306w, 1255m, 1156m, 1133m, 1102m, 873m, 840m. 1H-NMR (300 MHz,
CDCl3): see Table 3; additionally, 1.48, 1.39 (2s, Me2C); 0.93( s, Me3C); 0.18 (s, Me2Si); 0.16 (s, Me2Si). 13C-NMR
(150 MHz, CDCl3): see Table 3; additionally, 113.66 (s, Me2C); 27.35, 26.06 (2q, Me2C); 25.72 (q, Me3C); 18.39 (s,
‡
‡
Me3C); À 4.43, À 4.71 (2q, Me2Si). EI-MS: 351 ([M ‡ K] ); 335 ([M ‡ Na] ). Anal. calc. for C14H24N2O4Si
(312.44): C 53.82, H 7.74, N 8.97; found: C 53.91, H 7.65, N 8.89.
Oxidation of 4 with Pb(OBz)4 [94]. a) A soln. of 4 (158 mg, 0.5 mmol) in CH2Cl2 (4 ml) was treated with a
soln. of Pb(OBz)4 (1.04 g, 1.5 mmol) in CH2Cl2 (10 ml), stirred at r.t. for 1 h, treated with H2O, and extracted
with Et2O (3 Â 30 ml). The combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt 20 :1 !
2 :1) gave 12 (46 mg, 23%) and 11 (23mg, 15%).

Helvetica Chimica Acta Vol. 87 (2004)
2423
b) A soln. of 4 (316 mg, 1.0 mmol) in toluene (5 ml) was treated with a soln. of Pb(OBz)4 (2.08 g, 3.0 mmol)
in toluene (25 ml), stirred at r.t. for 2 h, treated with H2O, and extracted with Et2O (3 Â 30 ml). The combined
org. layers were dried and evaporated. FC (cyclohexane/AcOEt 20 :1 ! 2 :1) gave 12 (134 mg, 33%) and 11
(130 mg, 42%).
Data of 2D-(1,5/1,2,3,4)-1,5-Anhydro-1-O-benzoyl-4-O-[(tert-butyl)dimethylsilyl]-2,3-O-isopropylidene-
cyclopentane-1,1,2,3,4,5-hexol (12). White crystals. M.p. 114 1158 (MeOH). Rf (cyclohexane/AcOEt 4 :1)
0.74. [a]2D5 ˆ ‡25.9 (c ˆ 0.58, CHCl3). IR (CHCl3): 2991w, 2954m, 2931m, 2897w, 2886w, 2858m, 1745s, 1601w,
1472w, 1463w, 1453w, 1383m, 1375m, 1362w, 1316w, 1271s, 1259s, 1234s, 1158m, 1137s, 1090s, 1064s, 1026m, 999w,
866m, 83 8s. 1H-NMR (300 MHz, CDCl3): see Table 3; additionally, 8.12 8.04 (m, 2 arom. H); 7.64 7.55 (m, 1
arom. H); 7.50 7.41 (m, 2 arom. H); 1.49, 1.36 (2s, Me2C); 0.95 (s, Me3C); 0.151, 0.146 (2s, Me2Si). 13C-NMR
(75 MHz, CDCl3): see Table 3; additionally, 165.08 (s, CˆO); 133.88 (d); 130.28 (2d); 128.77 (s); 128.55 (2d);
113.59 (s, Me2C); 26.93( q, Me2C); 26.15 (q, Me3C); 18.82 (s, Me3C); À 4.27, À 4.92 (2q, Me2Si). HR-MALDI-
‡
‡
MS: 429.1703(78, [ M ‡ Na] ; C21H30NaO6Si ; calc. 429.1704). Anal. calc. for C21H30O6Si (406.55): C 62.04, H
7.44; found: C 62.13, H 7.37.
Crystal Structure of 12. Recrystallization of 12 in MeOH gave crystals suitable for X-ray analysis,
C21H30O6Si (406.55); orthorhombic P212121; a ˆ 6.8920 (3) ä, b ˆ 18.0783(8) ä, c ˆ 18.5672 (8) ä, b ˆ 908; Vˆ
2313.4 (2) ä3; Dcalc. ˆ 1.167 Mg/m3; Z ˆ 4. From a crystal of size 0.4  0.24  0.2 mm, 4897 reflections were
measured on an KappyCCD diffractometer with MoKa radiation (graphite monochromator, l ˆ 0.71073ä) at
298 K. R ˆ 0.0983, Rw ˆ 0.2184. The structure was solved by direct method with SIR-97. The non-H-atoms were
refined anisotropically with SHELXS-97.
1d-(1,2,3,4/5)-4-O-[(tert-Butyl)dimethylsilyl]-2,3-O-isopropylidenecyclopentane-1,2,3,4,5-pentol (28). A
soln. of 10 (578 mg, 1.68 mmol) in THF (12 ml) was cooled to 08, treated with LiAlH4 (114 mg, 3.36 mmol)
in portions, stirred for 2 h, and cautiously poured into ice/H2O (20 ml). After extraction with CH2Cl2 (4 Â
50 ml), the combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt 2 :1) gave 28 as a
colourless syrup (410 mg, 80.5%), which crystallized upon standing. White crystals. M.p. 65.0 66.58. Rf
(cyclohexane/AcOEt 2 :1) 0.10. [a]2D5 ˆ ‡31.3 (c ˆ 0.55, CHCl3). IR (CHCl3): 3611w, 3540w (br.), 3019s,
1
2932m, 2859m, 1473w, 1384m, 1259m, 1162s, 1107s, 1028m, 981w, 876s, 83 9s. H-NMR (300 MHz, CDCl3): see
Table 4; additionally, 3.88 (addition of D2O ! t, J ˆ 8.7, HÀC(5)); 3.59 (irrad. at 4.44 ! t, J ˆ 9.9, addition of
D2O ! dd, J ˆ 9.7, 5.6, HÀC(1)); 2.63( d, J ˆ 9.7, exchanged with D2O, HOÀC(1)); 2.46 (br. d, J ˆ 2.2,
1
Table 4. Chemical Shifts [ppm] and Coupling Constants [Hz] for the Cyclopentyl H- and 13C-NMR Signals of
the Cyclopentane Derivatives 28 37 in CDCl3
28a)
29a)
30
4.72
4.78
4.48
3.80
4.41
31
4.61
4.57
4.44
3.69
4.34
5.6
32
4.78
4.634.54
4.50
3.96
5.14
5.6
33a)b)
34a)b)
35b)
36b)
37b)
HÀC(1)
HÀC(2)
HÀC(3)
HÀC(4)
HÀC(5)
J(1,2)
3.59
4.44
4.41
3.60
3.88
5.6
5.8
5.35.0
9.0
4.97
4.87
4.57
4.17
6.02
5.9
3.34
3.41
3.36
3.52
4.58
4.97
5.09
5.35
0
5.6
5.8
9.0
6.2
3.55
4.56
44.6.537
4.68
4.47
4.22
4.95
0.6
4.74
3.58
3.62
0
4.63 4.57
4.23
4.97
4.82
5.25
4.61
2.2
5.6
5.6
c
5.6
5.0
)
)
)
c
c
J(2,3)
5.6
5.6
5.6
6.2
6.5
,4)J(3
5.0
5.35.35.3 1.6
8.7
J(4,5)
J(5,1)
9.0
9.0
9.0
8.4
9.0
8.4
8.1
6.2
2.2
0
8.1
6.2
8.0
2.0
10.0
8.4
28a)
29a)
30
31
32
33a)b)
34a)b)
35b)
36b)
37b)
C(1)
C(2)
C(3)
C(4)
C(5)
73.23
75.42
77.55
74.37
79.54
74.16
74.31
77.96
72.28
77.96
75.96
74.23
77.98
74.31
76.75
86.58
73.19
78.03
74.16
76.26
84.29
73.87
77.56
71.19
83.53
50.39
82.27
75.77
74.41
85.37
48.62
85.82
79.46
58.37
61.59
50.26
81.86
74.85
73.40
85.54
49.17
81.83
72.67
79.08
82.37
53.07
80.29d)
79.61 d)
86.39e)
85.15e)
a) Assignment based on a 1H,13C-COSY spectrum. b) Arbitrary numbering as for 28. c) Not assigned.
d
)
e) Assignments may be interchanged.

2424
Helvetica Chimica Acta Vol. 87 (2004)
exchanged with D2O, HOÀC(5)); 1.48, 1.32 (2s, Me2C); 0.92 (s, Me3C); 0.12 (s, Me2Si). 13C-NMR (75 MHz,
CDCl3): see Table 4; additionally, 111.40 (s, Me2C); 25.95 (q, Me3C, MeC); 24.28 (q, MeC); 18.41 (s, Me3C);
‡
‡
À 4.50, À 4.55 (2q, Me2Si). ESI-MS: 327 (79, [M ‡ Na] ), 305 (100, [M ‡ H] ). HR-MALDI-MS: 327.1595
‡
‡
(100, [M ‡ Na] ; C14O28O5NaSi ; calc. 327.1598). Anal. calc. for C14O28O5Si (304.46): C 55.23, H 9.27; found: C
55.19, H 9.10.
1d-(1,2,3,4/5)-1,5-Di-O-benzoyl-4-O-[(tert-butyl)dimethylsilyl]-2,3-O-isopropylidenecyclopentane-
1,2,3,4,5-pentol (29) and 1d-(1,2,3,4/5)-1-O-Benzoyl-4-O-[(tert-butyl)dimethylsilyl]-2,3-O-isopropylidenecyclo-
pentane-1,2,3,4,5-pentol (30). A soln. of 28 (300 mg, 0.98 mmol) in CH2Cl2 (25 ml) was cooled to À 408, treated
with TMEDA (300 ml, 2.0 mmol) and BzCl (100 ml, 0.86 mmol), and stirred for 30 h. In regular intervals,
additional TMEDA and BzCl (a total of 450 ml, 3.0 mmol TMEDA and 200 ml, 1.7 mmol BzCl) were added until
TLC showed completion of the reaction. The mixture was treated with brine (20 ml), extracted with CH2Cl2
(3 Â 30 ml), and dried. Evaporation and FC (hexane/AcOEt 12 :1) gave 29 (132 mg, 26 %) and 30 (265 mg,
67%).
Data of 29. White crystals. M.p. 161.5 1638 (benzene). Rf (hexane/AcOEt 4 :1) 0.48. [a]2D5 ˆ À64.6 (c ˆ 0.5,
CHCl3). IR (CHCl3): 2940m, 2858w, 1719s, 1452w, 1384w, 1372w, 1261s, 1108s, 873m, 841m. 1H-NMR (500 MHz,
CDCl3): see Table 4; additionally, 8.09 8.02 (m, 4 arom. H); 7.56 7.52 (m, 2 arom. H); 7.44 7.39 (m, 4 arom.
H); 1.54, 1.32 (2s, Me2C); 0.85 (s, Me3C); 0.11, 0.02 (2s, Me2Si). 13C-NMR (125 MHz, CDCl3): see Table 4;
additionally, 166.27, 165.48 (2s, 2 CˆO); 133.12, 133.00 (2d); 129.98 (2d); 129.90 (s); 129.68 (2d); 129.42 (s);
128.34 (2d); 128.31 (2d); 112.15 (s, Me2C); 26.01, 24.95 (2q, Me2C); 25.61 (q, Me3C); 18.17 (s, Me3C); À 4.69,
‡
À 4.83(2 q, Me2Si). MALDI-MS: 535 (100, [M ‡ Na] ). Anal. calc. for C28H36O7Si (512.67): C 65.60, H 7.08;
found: C 65.64, H 6.87.
Data of 30. White crystals. M.p. 100.5 1018. Rf (hexane/AcOEt 4 :1) 0.31. [a]2D5 ˆ À31.7 (c ˆ 0.54, CHCl3).
IR (CHCl3): 3609w, 2954m, 2935m, 2861w, 1717s, 1472w, 1444w, 1372w, 1265s, 1122s, 1028w, 877s, 841s. 1H-NMR
(300 MHz, CDCl3): see Table 4; additionally, 8.15 8.05 (m, 2 arom. H); 7.56 (m, 1 arom. H); 7.48 7.40 (m, 2
arom. H); 2.40 (br. s, exchanged with D2O, HOÀC(5)); 1.45, 1.28 (2s, Me2C); 0.95 (s, Me3C); 0.16, 0.15 (2s,
Me2Si). 13C-NMR (75 MHz, CDCl3): see Table 4; additionally, 166.80 (s, CˆO); 133.18 (d); 129.95 (2d); 129.79
(s); 128.38 (2d); 111.65 (s, Me2C), 25.83, 24.60 (2q, Me2C); 25.73( q, Me3C); 18.21 (s, Me3C); À 4.73( q, Me2Si).
‡
‡
HR-MALDI-MS: 431.1859 (100, [M ‡ Na] , C21H32NaO6Si ; calc. 431.1860). Anal. calc. for C21H32O6Si
(408.57): C 61.74, H 7.89; found: C 61.78, H 7.65.
Crystal Structure of 30. Recrystallization of 30 in benzene gave crystals suitable for X-ray analysis,
C28H36O7Si (512.67); monoclinic P21; a ˆ 6.3780 (10) ä, b ˆ 19.449 (5) ä, c ˆ 11.752 (3) ä, b ˆ 103.00 (2)8; Vˆ
1420.4 (4) ä3; Dcalc. ˆ 1.199 Mg/m3; Z ˆ 2. From a crystal of size 0.35  0.08  0.08 mm, 2283reflections were
measured on an Enraf Nonius CAD-4 diffractometer with CuKa radiation (graphite monochromator, l ˆ
1.54184 ä) at 293K. R ˆ 0.0863, Rw ˆ 0.1632. The H-atoms were calculated at idealized positions and included in
the structure-factor calculation with fixed isotropic displacement parameters.
1d-(1,2,3,4/5)-4-O-[(tert-Butyl)dimethylsilyl]-2,3-O-isopropylidene-1-O-[(trifluromethyl)sulfonyl]cyclo-
pentane-1,2,3,4,5-pentol (31). A soln. of 28 (410 mg, 1.35 mmol) in CH2Cl2 (40 ml) was cooled to À 608, treated
with pyridine (2.5 ml) and Tf2O (245 ml, 1.48 mmol), stirred for 1 h, treated slowly with more Tf2O (200 ml,
1.2 mmol), and stirred for 5 h when TLC showed completion of the reaction. The mixture was treated with H2O
(20 ml), warmed to r.t., and extracted with CH2Cl2 (3 Â 30 ml). The combined org. layers were dried and
evaporated. FC (hexane/AcOEt 8 :1) gave 31 (550 mg, 91%). Colourless syrup Rf (hexane/AcOEt 4 :1) 0.60.
[a]2D5 ˆ À20.5 (c ˆ 1.1, CHCl3). IR (CHCl3): 3620w, 3580w (br.), 3033w, 2931m, 2859m, 1472w, 1463w, 1416s,
1385m, 1375m, 1246s, 1226s, 1202s, 1163s, 1144s, 1098m, 994s, 876s, 83 7s, 615m. 1H-NMR (300 MHz, CDCl3): see
Table 4; additionally, 4.44 (addition of D2O and irrad. at 3.69 ! d, J ˆ 4.8, HÀC(3)); 4.34 (addition of D2O ! t,
J ˆ 8.4, addition of D2O and irrad. at 3.69 ! d, J ˆ 8.4, HÀC(5)); 2.52 (d, J ˆ 4.4, exchanged with D2O,
HOÀC(5)); 1.49, 1.33 (2s, Me2C); 0.92 (s, Me3C); 0.123, 0.120 (2s, Me2Si). 13C-NMR (75 MHz, CDCl3): see
Table 4; additionally, 118.63( q, J ˆ 317.5, CF3); 112.70 (s, Me2C), 26.03( q, Me3C, MeC); 24.81 (q, MeC); 18.58
‡
‡
‡
(s, Me3C); À 4.31 (q, Me2Si). ESI-MS: 475 (10.5, [M ‡ K] ), 459 (100, [M ‡ Na] ), 437 (2, [M ‡ H] ). Anal.
calc. for C15H27F3O7SSi (436.52): C 41.27, H 6.23, F 13.06, S 7.35; found: C 41.47, H 6.04, F 12.95, S 7.40.
1d-(1,2,3,4/5)-4-O-[(tert-Butyl)dimethylsilyl]-2,3-O-isopropylidene-5-O-(methylsulfonyl)-1-O-[(trifluoro-
methyl)sulfonyl]cyclopentane-1,2,3,4,5-pentol (32). A soln. of 31 (534 mg, 1.23 mmol) in CH2Cl2 (15 ml) was
cooled to 08, treated with pyridine (2.0 ml) and Ms2O (426 mg, 2.44 mmol), stirred for 3h at 0 8 and for 2 h at 238,
treated with H2O (15 ml), and extracted with CH2Cl2 (3 Â 30 ml). The combined org. layers were dried and
evaporated. FC (hexane/AcOEt 4 :1) gave 32 (625 mg, 99%). Colourless syrup. Rf (hexane/AcOEt 4 :1) 0.44.
[a]2D5 ˆ À9.7 (c ˆ 1.2, CHCl3). IR (CHCl3): 3035w, 2933m, 2860w, 1473w, 1464w, 1421s, 1376s, 1334w, 1247s,
1182s, 1163m, 1143s, 1101m, 1034s, 1000s, 966s, 882s, 83 s7. 1H-NMR (300 MHz, CDCl3): see Table 4;

Helvetica Chimica Acta Vol. 87 (2004)
2425
additionally, 5.14 (irrad. at 3.96 ! d, J ˆ 8.4, HÀC(5)); 4.78 (irrad. at 5.14 ! d, J ˆ 6.0, HÀC(1)); 4.50 (irrad. at
3.96 ! d, J ˆ 5.4, HÀC(3)); 3.96 (irrad. at 5.14 ! d, J ˆ 4.8, HÀC(4)); 3.07 (s, MsO); 1.55, 1.35 (2s, Me2C); 0.92
(s, Me3C); 0.14, 0.13(2 s, Me2Si). 13C-NMR (75 MHz, CDCl3): see Table 4; additionally, 118.51 (q, J ˆ 319.2,
CF3); 113.34 (s, Me2C), 39.11 (q, MsO); 26.03, 24.89 (2q, Me2C); 25.91 (q, Me3C); 18.44 (s, Me3C); À 4.38,
‡
À 4.43(2 q, Me2Si). MALDI-MS: 537 (100, [M ‡ Na] ). Anal. calc. for C16H29F3O9S2Si (514.61): C 37.34, H 5.68,
F 11.08, S 12.46; found: C 37.63, H 5.81, F 11.29, S 12.58.
1d-(1,2,3/4,5)-3-O-[(tert-Butyl)dimethylsilyl]-1,2-O-isopropylidene-5-(methylsulfanyl)-4-O-(methylsulfo-
nyl)cyclopentane-1,2,3,4-tetrol (33). A soln. of 32 (598 mg, 1.16 mmol) and 15-crown-5 (510 mg, 2.32 mmol) in
THF (40 ml) was treated with NaSMe (812 mg, 11.6 mmol), stirred at 238 for 2 h, treated with H2O (20 ml), and
extracted with CH2Cl2 (3 Â 30 ml). The combined org. layers were dried and evaporated. FC (cyclohexane/
AcOEt 8 :1) gave 33 (450 mg, 94%). White crystals. M.p. 92.5 938 (hexane). Rf (cyclohexane/AcOEt 4 :1) 0.41.
[a]2D5 ˆ ‡91.8 (c ˆ 0.5, CHCl3). IR (CHCl3): 3018w, 2932m, 2859w, 1473w, 1364s, 1254m, 1178s, 1094m, 1022m,
965m, 893m, 862s, 840s. 1H-NMR (300 MHz, CDCl3): see Table 4; additionally, 4.95 (irrad. at 3.34 ! d, J ˆ 8.1,
irrad. at 4.22 ! d, J ˆ 6.2, HÀC(4)); 4.54 (br. d, J ꢀ 6.2, irrad. at 3.34 ! sharp d, J ˆ 5.9, HÀC(1)); 4.47 (irrad. at
4.22 ! d, J ˆ 5.9, HÀC(2)); 4.22 (irrad. at 4.95 ! d, J ˆ 5.3, HÀC(3)); 3.34 (irrad. at 4.95 ! d, J ˆ 0.9,
HÀC(5)); 3.08 (s, MsO); 2.23( s, MeS); 1.47, 1.30 (2s, Me2C); 0.92 (s, Me3C); 0.13, 0.12 (2s, Me2Si). 13C-NMR
(75 MHz, CDCl3): see Table 4; additionally, 111.93( s, Me2C), 38.49 (q, MsO); 26.41, 24.71 (2q, Me2C); 26.04 (q,
‡
Me3C); 18.51 (s, Me3C); 16.09 (q, MeS); À 4.29, À 4.42 (2q, Me2Si). ESI-MS: 451 (14, [M ‡ K] ), 435 (12, [M ‡
‡
‡
Na] ), 413(18, [ M ‡ H] ), 355 (100). Anal. calc. for C16H32O6S2Si (412.64): C 46.57, H 7.82, S 15.54; found: C
46.74, H 7.79, S 15.58.
1d-(1,2,3,4/5)-3,4-Anhydro-1,2-O-isopropylidene-5-(methylsulfanyl)cyclopentane-1,2,3,4-tetrol (34) and
1d-(1,2,3/4,5)-1,2-O-Isopropylidene-5-(methylsulfanyl)-4-O-(methylsulfonyl)cyclopentane-1,2,3,4-tetrol (35). a)
A soln. of 33 (289 mg, 0.7 mmol) in THF (30 ml) was cooled to 08, treated with 1m TBAF in THF (735 ml,
0.735 mmol), stirred at 08 for 5 min, treated with sat. aq. NH4Cl (10 ml), and extracted with CH2Cl2 (3 Â 3 0 ml).
The combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt 4 :1 ! 1:1) gave 34 (42 mg,
30%) and 35 (137 mg, 66%).
b) A soln. of 33 (358 mg, 0.87 mmol) in THF (16 ml) was cooled to À 308, treated with 1 M TBAF in THF
(960 ml, 0.96 mmol), stirred for 2.5 h, treated with sat. aq. NH4Cl soln. (10 ml) at À 308, warmed to r.t., and
extracted with CH2Cl2 (3 Â 30 ml). The combined org. layers were dried and evaporated. FC (cyclohexane/
AcOEt 4 :1 ! 1:1) gave 35 (257 mg, 99%).
Data of 34. Rf (hexane/AcOEt 4 :1) 0.49. [a]2D5 ˆ À14.0 (c ˆ 0.5, CHCl3). IR (neat): 2990w, 2978w, 2953w,
2930w, 2915w, 2856w, 1453w, 1429w, 1381m, 1370m, 1267m, 1253m, 1223m, 1203s, 1159m, 1114w, 1071s, 1056s,
1
1031m, 994m, 958m, 93 9w, 892m, 853s, 846s, 83 0s. H-NMR (300 MHz, CDCl3): see Table 4; additionally, 4.74
(irrad. at 4.56 ! d, J ˆ 1.5, HÀC(2)); 4.56 (br. d, J ꢀ 6.5, irrad. at 4.74 ! br. s, HÀC(1)); 3.62 (irrad. at 4.56 ! d,
J ˆ 2.7, HÀC(4)); 3.58 (irrad. at 4.74 ! d, J ˆ 2.4, H ÀC(3)); 2.18 (s, MeS); 1.52, 1.28 (2s, Me2C). 13C-NMR
(75 MHz, CDCl3): see Table 4; additionally, 112.90 (s, Me2C); 26.33, 25.46 (2q, Me2C); 14.64 (q, MeS). ESI-MS:
‡
203(100, [ M ‡ H] ).
Data of 35. Rf (cyclohexane/AcOEt 2:1) 0.16. [a]2D5 ˆ ‡89.0 (c ˆ 0.5, CHCl3). IR (CHCl3): 3547w (br.),
3032w, 2994w, 2940w, 1456w, 1361s, 1264w, 1230m, 1176vs, 1112m, 1067s, 1022s, 966s, 921w, 886m, 864m, 840m.
1H-NMR (300 MHz, CDCl3): see Table 4; additionally, 4.97 (irrad. at 4.23 ! d, J ˆ 5.9, irrad. at 3.36 ! d, J ˆ 8.1,
HÀC(4)); 4.23(br. s, addition of D2O ! m, HÀC(3)); 3.17 (s, MsO); 2.76 (br. d, J ˆ 7.6, exchanged with D2O,
HOÀC(3)); 2.23 (s, MeS); 1.50, 1.34 (2s, Me2C). 13C-NMR (75 MHz, CDCl3): see Table 4; additionally, 112.19
‡
(s, Me2C), 38.97 (q, MsO); 26.18, 24.28 (2q, Me2C); 16.12 (q, MeS). ESI-MS: 337 (16, [M ‡ K] ), 321 (100,
‡
[M ‡ Na] ). Anal. calc. for C10H18O6S2 (298.38): C 40.25, H 6.08, S 21.49; found: C 40.25, H 6.13, S 21.50.
1d-(1,2,3/4,5)-1,2-O-Isopropylidene-5-(methylsulfanyl)-4-O-(methylsulfonyl)-3-O-(2,2,2-trichloro-1-imi-
noethyl)cyclopentane-1,2,3,4-tetrol (36). A soln. of 35 (27 mg, 0.09 mmol) in CH2Cl2 (5 ml) was treated with
Cl3CCN (130 mg, 0.9 mmol) and DBU (15 mg, 0.1 mmol), and stirred at 238 for 1 h. Evaporation and FC
(cyclohexane/CH2Cl2 2 :1 ! cyclohexane/AcOEt 4 :1) gave 36 (40 mg, 100%). White crystals. M.p. 96.5 98.58
(hexane/Et2O). Rf (cyclohexane/AcOEt 4 :1) 0.33. [a]2D5 ˆ ‡96.7 (c ˆ 0.31, CHCl3). IR (CHCl3): 3346w, 3030w,
2995w, 2939w, 2926w, 1669s, 1602w, 1368vs, 1315m, 1289m, 1255m, 1178s, 1088s, 1054s, 1024m, 968s, 868m, 83 3s.
1H-NMR (300 MHz, CDCl3): see Table 4; additionally, 8.52 (br. s, CˆNH); 5.35 (irrad. at 3.52 ! d, J ˆ 9.0,
HÀC(4)); 4.97 (irrad. at 4.68 ! d, J ˆ 5.6, HÀC(2)); 3.13 (s, MsO); 2.30 (s, MeS); 1.47, 1.31 (2s, Me2C).
13C-NMR (75 MHz, CDCl3): see Table 4; additionally, 161.06 (s, CˆN); 112.07 (s, Me2C); 90.57 (s, Cl3C); 38.45
‡
(q, MsO); 26.21, 24.67 (2q, Me2C); 16.28 (q, MeS). ESI-MS: 486 (5), 484 (21), 482 (51), 480 (41, [M ‡ K] ), 470
‡
(9), 468 (37), 466 (100), 464 (94, [M ‡ Na] ). Anal. calc. for C12H18Cl3NO6S2 (442.77): C 32.55, H 4.10, Cl 24.02,
N 3.16, S 14.48; found: C 32.75, H 4.11, Cl 23.93, N 3.04, S 14.31.

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Helvetica Chimica Acta Vol. 87 (2004)
1d-(1,2,3,4/5)-4-Amino-1,2-O-isopropylidene-5-(methylsulfanyl)-3-O,4-N-(2,2,2-trichloroethylidyne)cyclo-
pentane-1,2,3-triol (37). a) A soln. of 36 (93mg, 0.21 mmol) in xylene (10 ml) was treated with EtN(i-Pr) 2
(0.2 ml), stirred at 1108 for 24 h, cooled to r.t., treated with H2O (10 ml), and extracted with Et2O (3 Â 10 ml).
The combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt 8 :1 ! 1:1) gave 37 (26 mg,
33%).
b) A soln. of 35 (210 mg, 0.7 mmol) in xylene (30 ml) was treated with Cl3CCN (0.7 ml, 7.0 mmol) and
DBU (120 mg, 0.77 mmol), stirred at 238 for 2 h, treated with EtN(i-Pr)2 (1.18 ml), heated to 1108, stirred for
12 h, cooled to r.t., treated with H2O (20 ml), and extracted with Et2O (2 Â 30 ml). The combined org. layers
were dried and evaporated. FC (cyclohexane/AcOEt 12 :1) gave 37 (193mg, 80%) and 36 (41 mg, 13%).
Data of 37. White crystals from hexane/Et2O. M.p. 88 88.58. Rf (cyclohexane/AcOEt 4 :1) 0.44. [a]D25
ˆ
‡22.0 (c ˆ 0.52, CHCl3). IR (CHCl3): 3029w, 2996m, 2941w, 2923w, 1653s, 1456w, 1434w, 1385m, 1377m, 1311m,
1266m, 1240m, 1200m, 1157m, 1105m, 1059vs, 1005m, 966w, 878m, 836vs, 814s. 1H-NMR (300 MHz, CDCl3): see
Table 4; additionally, 5.25 (irrad. at 3.55 ! dd, J ˆ 8.4, 5.9, HÀC(3)); 4.61 (irrad. at 3.55 ! d, J ˆ 8.3, HÀC(4));
4.58 (irrad. at 3.55 ! d, J ˆ 5.6, HÀC(1)); 2.25 (s, MeS); 1.49, 1.33 (2s, Me2C). 13C-NMR (75 MHz, CDCl3): see
Table 4; additionally, 162.10 (s, CˆN); 112.93( s, Me2C); 26.53, 24.41 (2q, Me2C); 15.58 (q, MeS); s for CCl3
‡
hidden by the noise. ESI-MS: 352 (4), 350 (35), 348 (100), 346 (96, [M ‡ H] ). Anal. calc. for C11H14Cl3NO3S
(346.66): C 38.11, H 4.07, Cl 30.68, N 4.04, S 9.25; found: C 38.32, H 4.30, Cl 30.61, N 4.04, S 9.20.
1l-(1,2,3,4/5)-2,3,4-Trihydroxy-5-(methylsulfanyl)cyclopentane-1-ammonium Chloride (1 ¥ HCl; (‡)-Man-
nostatin A hydrochloride) [57]. A suspension of 37 (33 mg, 0.095 mmol) in 7n HCl/MeOH 1:1 (5 ml) was
stirred at 238 for 3h. The mixture was coevaporated with toluene. A soln. of the residue in H 2O was washed with
CH2Cl2 and Et2O. Evaporation of the aq. layer gave 1 ¥ HCl (19 mg, 93%). [a]2D5 ˆ ‡7.5 (c ˆ 0.95, MeOH) ([39]:
[a]D ˆ 5.9 (c ˆ 1.08, MeOH); [42]: [a]2D1 ˆ 6 (c ˆ 0.46, MeOH)). 1H-NMR (300 MHz, D2O): 4.15 (dd, J ˆ 6.2, 4.0,
HÀC(4)); 3.96 (t, J ꢀ 4.3, HÀC(3)); 3.87 (dd, J ˆ 7.5, 4.7, HÀC(2)); 3.41 (t, J ꢀ 6.8, HÀC(5)); 2.98 (t, J ꢀ 7.3,
HÀC(1)); 2.01 (s, MeS). 13C-NMR (75 MHz, D2O): 73.71, 72.06, 68.25 (3d, C(2), C(3), C(4)); 55.00 (d, C(1));
51.73( d, C(5)); 12.10 (q, MeS).
1d-(1,2,3,4/5)-4-Amino-5-(methylsulfanyl)cyclopentane-1,2,3-triol (1; (‡)-Mannostatin A) [57]. a) A
suspension of 37 (45 mg, 0.13mmol) in 7 n HCl/MeOH 1:1 (7 ml) was stirred at 238 for 3h. The mixture
was co-evaporated with toluene. Filtration of the residue through a small column packed with Amberlite IR-120
‡
(H form, 0.5n NH3) gave 1 (19 mg, 81.5% from 37).
b) Filtration of 1 ¥ HCl (18 mg, 0.084 mmol) in H2O (5 ml) through a small column packed with Amberlite
‡
IR-120 (H form, 0.5n NH3) gave 1 (12 mg, 80%).
Biological activity: synthetic 1 inhibited jack bean a-d-mannosidase with IC50 ˆ 48 nm; (p-nitrophenyl a-d-
mannopyranoside, acetate buffer, pH 4.5)
1d-(1,2,3,4/5)-4-Acetamido-1,2,3-tri-O-acetyl-5-(methylsulfanyl)cyclopentane-1,2,3-triol (38; (‡)-Tetraace-
tylmannostatin A) [6]. A suspension of 37 (28 mg, 0.081 mmol) in 7n HCl/MeOH 1:1 (5 ml) was stirred at 238
for 1 h. The mixture was co-evaporated with toluene. A soln. of the residue in pyridine (1 ml) was cooled to 08,
treated with Ac2O (153 ml, 1.62 mmol) for 3h, diluted with H 2O, and extracted with CH2Cl2 (3 Â 10 ml). The
combined org. layers were dried (MgSO4) and evaporated. FC (cyclohexane/AcOEt 1:2) gave 38 (26 mg, 93%
from 37). White crystals from hexane/AcOEt. M.p. 121.5 122.58 ([6]: m.p. 1218; [30]: m.p. 119 1208; [42]:
122 1238). Rf (cyclohexane/AcOEt 4 :1) 0.41. [a]2D5 ˆ ‡18.3( c ˆ 1.02, CHCl3); [30]: [a]D ˆ ‡8.5 (c ˆ 0.9,
CHCl3); [95]: [a]2D8 ˆ ‡7.4 (c ˆ 0.45, CHCl3); [42]: [a]D27 ˆ ‡16 (c ˆ 0.88, CHCl3)). IR (neat): 3304w, 3061w,
2985w, 2954w, 2924w, 1735vs, 1647m, 1535m, 1435w, 1374m, 1360m, 1283w, 1250s, 1230s, 1219s, 1084s, 1014m,
1
929m, 912m, 873w, 822w. H-NMR (300 MHz, CDCl3): 5.70 (d, J ˆ 9.3, NH); 5.39 (dd, J ˆ 6.0, 4.0, HÀC(2));
5.33 (d, J ˆ 5.6, 4.0, HÀC(3)); 5.16 (td, J ˆ 6.5, 0.6, HÀC(1)); 4.53(br. td, J ꢀ 9.0, 5.6, HÀC(4)); 3.10 (dd, J ˆ 8.1,
6.2, HÀC(5)); 2.16, 2.11, 2.07, 2.05, 2.04 (5s, 4 Ac, MeS). 13C-NMR (75 MHz, CDCl3): 169.53, 169.47, 169.23,
168.84 (4s, 4 CˆO); 73.85, 71.14, 70.46 (3d, C(1), C(2), C(3)); 53.29, 51.74 (2d, C(4), C(5)); 23.53, 20.86, 20.83,
‡
‡
20.70 (4q, 4 Me); 13.71 (q, MeS). HR-MALDI-MS: 370.0935 (100, [M ‡ Na] , C14H21NNaO7S ; calc. 370.0931);
‡
‡
‡
‡
348.1111 (43, [M ‡ H] , C14H22NO7S ; calc. 348.1112); 288.0897 (86, [M À AcO] , C12H18NO5S ; calc.
288.0900).
5-Deoxy-5-hydrazino-2,3-O-isopropylidene-d-lyxono-1,5-lactam (40). A suspension of 39 [59] (266 mg,
1.0 mmol) in NH2NH2 ¥ H2O (0.4 ml) was stirred at 238 for 3h. The resulting clear soln. was co-evaporated with
toluene (2 Â 30 ml). A soln. of the residue in CH2Cl2 (15 ml; formation of some crystals) was dried, and
evaporated to afford crude 40 (240 mg). Colourless oil. The crude was used for the next step. 1H-NMR
(200 MHz, CDCl3): see Table 5; additionally, 1.43, 1.38 (2s, Me2C). 13C-NMR (50 MHz, CDCl3): see Table 5;
additionally, 110.82 (s, Me2C); 27.08, 24.98 (2q, Me2C).

Helvetica Chimica Acta Vol. 87 (2004)
2427
Table 5. Selected 1H- and 13C-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the N-Amino-
glyconolactams in CDCl3
40
41
45
46
50
4.16
51
a
HÀC(2)
HÀC(3)
HÀC(4)
HÀC(5)
H'ÀC(5)
J(2,3)
J(3,4)
J(4,5)
J(4,5')
J(5,5')
4.634.55 34.80 4.724.3
)
4.07
3.76
3.94
3.61
3.34
7.1
4.39
4.14
3.89
3.53
6.2
4.22
4.06
3.82
3.36
6.2
3.90
4.30
3.63
3.54
6.8
2.2
4.6
5.3
12.4
3.89
4.30
3.52
3.52
6.5
3.69
3.93
3.74
3.39
7.5
4.2b)
2.5
4.0b)
2.5
1.9
7.5
7.1
5.35.4
5.3
4.7
4.2
13.3
3.7
13.1
7.6
12.0
7.1
12.5
c
)
40
41
45
46
51
C(1)
C(2)
C(3)
C(4)
C(5)
166.22
73.93
76.85
66.69
53.14
166.35
74.25
77.07
67.26
53.66
166.63
73.05
78.87
64.87
53.11
166.64
73.40
76.01
66.09
54.28
168.20
74.53
79.60
68.79
54.88
a) Signal overlapping with MOM signals. b) J(3,5') ˆ 1.2 Hz. c) Not assigned.
4-O-[(tert-Butyl)dimethylsilyl]-5-deoxy-5-hydrazino-2,3-O-isopropylidene-d-lyxono-1,5-lactam (41).
TBSOTf (0.56 ml, 2.4 mmol) was added dropwise to a cooled (08) soln. of crude 40 (240 mg) in CH2Cl2
(2 ml) and pyridine (0.6 ml). The mixture was stirred at 08 for 1 h and at r.t. for 3h, treated with H 2O (10 ml),
extracted with CH2Cl2 (3 Â 50 ml), and dried. Evaporation and FC (hexane/AcOEt 3:2) gave 41 (202 mg, 64%
from 39). White crystals M.p. 52 538. Rf (cyclohexane/AcOEt 1:2) 0.50. [a]2D6 ˆ ‡11.4 (c ˆ 0.45, CHCl3). IR
(CHCl3): 3449w (br.), 3320w, 3024w, 3016m, 2955m, 2931m, 2858m, 1655s, 1616w, 1471w, 1463w, 1385m, 1376m,
1257m, 1235m, 1162w, 1123s, 1095m, 1042w, 1006w, 93 7m, 866w, 83 9s, 825m, 810m. 1H-NMR (300 MHz, CDCl3):
see Table 5; additionally, 4.44 (s, exchanged with D2O, NH2); 1.38, 1.34 (2s, Me2C); 0.83( s, Me3C); 0.066, 0.063
(2s, 2 Me2Si). 13C-NMR (75 MHz, CDCl3): see Table 5; additionally, 110.72 (s, Me2C); 27.05, 25.09 (2q, Me2C);
‡
‡
25.67 (q, Me3C); 17.98 (s, Me3C); À 4.81 (2q, Me2Si). MALDI-MS: 339 (25, [M ‡ Na] ), 317 (53, [M ‡ H] ).
‡
‡
HR-MALDI-MS: 317.1885, (53, [M ‡ H] , C14H29N2O4Si ; calc. 317.1891). Anal. calc. for C14H28N2O4Si
(316.47): C 53.13, H 8.92, N 8.85; found: C 53.26, H 8.95, N 8.55.
5-O-[(2,4,6-Trimethylphenyl)sulfonyl]-d-arabino-1,4-lactone (43). A soln. of 42 (3.85 g, 26 mmol) and
−mesitylene-2-sulfonyl chloride× (MtsCl; 6.82 g, 31.2 mmol) in pyridine (20 ml) was stirred at 08 for 1 h and at 238
for 4 h. The mixture was treated with H2O (10 ml) and extracted with CH2Cl2 (3 Â 30 ml). Removal of the
solvent by co-evaporation with toluene and FC (cyclohexane/AcOEt 1:1) gave 43 (5.95 g, 69%). Colourless
syrup. Rf (hexane/AcOEt 1 :2) 0.46. [a]2D5 ˆ ‡59.4 (c ˆ 1.42, CHCl3). IR (CHCl3): 3564w (br.), 3368w (br.),
2981w, 2942w, 1798s, 1604m, 1450w, 1356s, 1167vs, 1139m, 1072m, 1036m, 920m. 1H-NMR (300 MHz, CDCl3):
6.99 (s, 2 arom. H); 4.54 (d, J ˆ 8.4, HÀC(2)); 4.42 (t, J ˆ 8.4, HÀC(3)); 4.34 (dt, J ˆ 8.4, 3.1, HÀC(4)); 4.25 (d,
J ˆ 3.1, 2 HÀC(5)); 2.60 (s, 2 Me); 2.31 (s, Me). 13C-NMR (75 MHz, CDCl3): 173.86 (s, CˆO); 144.01 (s); 140.16
(2s); 131.97 (2d); 129.45 (s); 77.77 (d, C(4)); 74.38, 73.46 (2d, C(2), C(3)); 66.31 (t, C(5)); 22.77 (q, 2 Me); 21.31
‡
(q, Me). MALDI-MS: 353 (100, [M ‡ Na] ). Anal. calc. for C14H18O7S (330.36): C 50.90, H 5.49, S 9.71; found:
C 50.80, H 5.63, S 9.60.
2,3-Bis-O-(methoxymethyl)-5-O-[(2,4,6-trimethylphenyl)sulfonyl]-d-arabino-1,4-lactone (44). A soln. of
43 (1.83g, 5.55 mmol) in CH 2(OMe)2 (4 ml) was added at r.t. to a suspension of P2O5 (1.0 g) in CH2(OMe)2
(1.0 ml). The mixture was stirred overnight, treated with ice/sat. NaHCO3 soln., and extracted with Et2O. The
org. layer was washed with brine, dried, and evaporated. FC (hexane/AcOEt 2 :1) gave 44 (1.99 g, 86%). White
needles M.p. 69 70.58. Rf (hexane/AcOEt 2 :1) 0.35. [a]2D5 ˆ ‡41.7 (c ˆ 1.0, CHCl3). IR (CHCl3): 2955w, 2901w,
2830w, 1802s, 1604w, 1567w, 1467w, 1452w, 1404w, 1362m, 1190s, 1175vs, 1153s, 1124m, 1078m, 1046vs, 976s,
919m, 814m. 1H-NMR (300 MHz, CDCl3): 6.96 (s, 2 arom. H); 4.97 (d, J ˆ 6.9), 4.75 (d, J ˆ 6.9), 4.72 (d, J ˆ 6.9),

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Helvetica Chimica Acta Vol. 87 (2004)
4.66 (d, J ˆ 6.9) (2 MeOCH2); 4.49 (d, J ˆ 7.5, HÀC(2)); 4.35 (ddd, J ˆ 7.2, 4.6, 2.5, HÀC(4)); 4.29 (dd, J ˆ 11.5,
2.2, HÀC(5)); 4.26 (t, J ˆ 7.4, HÀC(3)); 4.21 (dd, J ˆ 11.5, 4.4, H'ÀC(5)); 3.41, 3.35 (2s, 2 MeO); 2.60 (s, 2 Me);
2.29 (s, Me). 13C NMR (75 MHz, CDCl3): 170.97 (s, CˆO); 143.89 (s); 140.27 (2s); 131.93 (2d); 130.01 (s); 97.02,
96.08 (2t, 2 MeOCH2), 78.10, 77.65 (2d, C(2) and C(3)); 75.55 (d, C(4)); 65.94 (t, C(5)); 56.11, 56.00 (2q, 2
‡
MeO); 22.43( q, 2 Me); 20.92 (q, Me). MALDI-MS: 441 (100, [M ‡ Na] ). Anal. calc. for C18H26O9S (418.46): C
51.66, H 6.26, S 7.66; found: C 51.70, H 6.29, S 7.76.
5-Deoxy-5-hydrazino-2,3-bis-O-(methoxymethyl)-d-arabino-1,5-lactam (45). A suspension of 44 (1.99 g,
4.76 mmol) in NH2NH2 ¥ H2O (4 ml) was stirred at r.t. for 3h. After removal of NH 2NH2 ¥ H2O by co-
evaporation with toluene, a soln. of the residue in CH2Cl2 (100 ml; formation of some crystals) was dried and
evaporated to give crude 45 (1.88 g). Colourless oil. 1H-NMR (300 MHz, CDCl3): see Table 5; additionally, 5.06
(d, J ˆ 6.5), 4.80 (d, J ˆ 6.9), 4.77 (d, J ˆ 6.9), 4.76 (d, J ˆ 6.5) (2 MeOCH2); 3.44 (s, 2 MeO). 13C-NMR
(75 MHz, CDCl3): see Table 5; additionally, 97.41, 97.19 (2t, 2 MeOCH2); 56.02, 55.98 (2q, 2 MeO). MALDI-
‡
‡
‡
MS: 273(71, [ M ‡ Na] ), 187 (100). HR-MALDI-MS: 273.1056 (71, [M ‡ Na] , C9H18N2NaO6Si ; calc.
273.1057).
4-O-[(tert-Butyl)dimethylsilyl]-5-deoxy-5-hydrazino-2,3-bis-O-(methoxymethyl)-d-arabino-1,5-lactam
(46). A soln. of crude 45 (1.88 g) in CH2Cl2 (10 ml) and pyridine (3ml) was treated with TBSOTf (2.74 ml,
11.9 mmol). The mixture was stirred at 08 for 1 h and at r.t. for 3h, treated with H 2O (30 ml), extracted with
CH2Cl2 (3 Â 50 ml), and dried. Evaporation and FC (hexane/AcOEt 3:2) gave 46 (1.4 g, 81% from 44).
Colourless syrup. Rf (hexane/AcOEt 1:2) 0.30. [a]2D5 ˆ À95.8 (c ˆ 1.1, CHCl3). IR (CHCl3): 3486w (br.), 3319w,
3009m, 2955s, 2931s, 2897m, 2858m, 1651s, 1614w, 1472m, 1463w, 1442w, 1390w, 1362w, 1288w, 1256m, 1152s,
1140s, 1106s, 1039vs, 962w, 919m, 869m, 83 9s. 1H-NMR (300 MHz, CDCl3): see Table 5; additionally, 5.04 (d, J ˆ
6.2, MeOCH); 4.80 4.72 (m, HÀC(2), 2 MeOCH); 4.40 (br. s, exchange with D2O, NH2); 4.29 (d, J ˆ 6.2,
MeOCH); 3.45, 3.39 (2s, 2 MeO); 0.89 (s, Me3C); 0.12, 0.10 (2s, Me2Si). 13C-NMR (75 MHz, CDCl3): see
Table 5; additionally, 97.30, 96.21 (2t, 2 MeOCH2); 56.12, 55.85 (2q, 2 MeO); 25.86 (q, Me3C); 18.24 (s, Me3C);
‡
‡
‡
À 4.54, À 4.65 (2q, Me2Si). MALDI-MS: 387 (100, [M ‡ Na] ), 365 (28, [M ‡ H] ), 333 (83, [M À MeO] ), 301
(64). Anal. calc. for C15H32N2O6Si (364.51): C 49.43, H 8.85, N 7.69; found: C 49.52, H 8.66, N 7.63.
5-O-[(2,4,6-Trimethylphenyl)sulfonyl]-d-xylono-1,4-lactone (48). A soln. of 47 (330 mg, 2.23 mmol) and
MtsCl (537 mg, 2.45 mmol) in pyridine (1.5 ml) was stirred at 08 for 3h and at 23 8 overnight, treated with H2O
(10 ml) and extracted with CH2Cl2 (3 Â 30 ml). Removal of the solvents by co-evaporation with toluene,
followed by FC (cyclohexane/AcOEt 1:1) gave 48 (458 mg, 62%). Colourless syrup. Rf (cyclohexane/AcOEt
1:1) 0.27. [a]2D5 ˆ ‡51.3( c ˆ 1.0, CHCl3). IR (CHCl3): 3520w (br.), 3356w (br.), 3032w, 2944w, 1803m, 1604w,
1456w, 1359s, 1176s, 1097m, 1065m, 965m, 854m. 1H-NMR (300 MHz, CDCl3): 6.96 (s, 2 arom. H); 4.74 (dt, J ꢀ
7.5, 3.5, HÀC(4)); 4.66 (t, J ꢀ 7.5, HÀC(3)); 4.6 3.8 (br. s, exchanged with D2O, HOÀC(2), HOÀC(3)); 4.59
(d, J ˆ 7.8, HÀC(2)); 4.30 (dd, J ˆ 11.2, 4.0, HÀC(5)); 4.20 (dd, J ˆ 11.2, 2.8, H×ÀC(5)); 2.56 (s, 2 Me), 2.28 (s,
Me). 13C-NMR (CDCl3): 174.81 (s, CˆO); 143.95 (s); 140.17 (2s); 131.92 (2d); 129.32 (s); 76.62 (d, C(4)); 73.10,
‡
72.68 (2d, C(2), C(3)); 66.11 (t, C(5)); 22.46 (q, 2 Me); 21.00 (q, Me). MALDI-MS: 353 (100, [M ‡ Na] ). Anal.
calc. for C14H18O7S (330.36): C 50.90, H 5.49, S 9.71; found: C 50.98, H 5.53, S 9.66.
2,3-Bis-O-(methoxymethyl)-5-O-[(2,4,6-trimethylphenyl)sulfonyl]-d-xylono-1,4-lactone (49). A soln. of 48
(2.04 mg, 6.18 mmol) in CH2(OMe)2 (8 ml) was added to a suspension of P2O5 (3g) in CH 2(OMe)2 (6 ml) and
stirred at r.t. overnight. The mixture was treated with ice/sat. NaHCO3 soln. and extracted with Et2O. The org.
layer was washed with brine, dried, and evaporated. FC (hexane/AcOEt 2 :1) gave 49 (2.01 g, 78%). Colourless
oil. Rf (hexane/AcOEt 2 :1) 0.33. [a]2D5 ˆ ‡81.1 (c ˆ 1.0, CHCl3). IR (CHCl3): 3019w, 2956w, 2903w, 1800s,
1604w, 1452w, 1362m, 1176s, 1154s, 1115m, 1048s, 979m. 1H-NMR (300 MHz, CDCl3): 6.98 (s, 2 arom. H); 4.94
(d, J ˆ 6.9), 4.72 (d, J ˆ 6.9, 2 H), 4.71 (d, J ˆ 6.9) (2 MeOCH2); 4.80 4.76 (m, HÀC(4)); 4.46 4.40 (AB,
HÀC(2), HÀC(3)); 4.30 (dd, J ˆ 10.9, 3.4, HÀC(5)); 4.20 (dd, J ˆ 10.9, 5.0, H'ÀC(5)); 3.41, 3.35 (2s, 2 MeO);
2.62 (s, 2 Me); 2.31 (s, Me). 13C-NMR (CDCl3): 171.88 (s, CˆO); 144.04 (s); 140.40 (2s); 132.10 (2d); 130.19 (s);
97.22, 96.21 (2t, 2 MeOCH2); 77.67, 76.77 (2d, C(2), C(3)); 74.03 (d, C(4)); 66.04 (t, C(5)); 56.35, 56.21 (2q,
‡
2 MeO); 22.59 (q, 2 Me); 21.07 (q, Me). MALDI-MS: 441 (100, [M ‡ Na] ). Anal. calc. for C18H26O9S (418.46):
C 51.66, H 6.26, S 7.66; found: C 51.72, H 6.21, S 7.47.
5-Deoxy-5-hydrazino-2,3-bis-O-(methoxymethyl)-d-xylono-1,5-lactam (50). A suspension of 49 (688 mg,
1.65 mmol) in NH2NH2 ¥ H2O (1 ml) was stirred at r.t. for 48 h. After removal of NH2NH2 ¥ H2O by co-
evaporation with toluene, a soln. of the residue was dried and evaporated to afford crude 50 (480 mg).
Colourless oil. 1H-NMR (200 MHz, CDCl3): see Table 5; additionally, 5.09 (d, J ˆ 6.6, MeOCH); 4.84 4.74 (m,
3MeOC H); 4.43(br. s, exchanged with D2O, NH2); 3.45 (s, 2 MeO).
4-O-[(tert-Butyl)dimethylsilyl]-5-deoxy-5-hydrazino-2,3-bis-O-(methoxymethyl)-d-xylono-1,5-lactam
(51). A soln. of crude 50 (360 mg) in CH2Cl2 (4 ml) and pyridine (1 ml) was treated with TBSOTf (0.66 ml,

Helvetica Chimica Acta Vol. 87 (2004)
2429
2.88 mmol), stirred at 08 for 1 h and at r.t. for 3h, treated with H 2O (10 ml), and extracted with CH2Cl2 (3 Â
10 ml). The org. layer was dried and evaporated. FC (hexane/AcOEt 1 :1) gave 51 as a syrup (380 mg, 85% from
49), which crystallized at 58. Rf (hexane/AcOEt 1:1) 0.44. [a]2D5 ˆ ‡58.5 (c ˆ 0.37, CHCl3). IR (neat): 3316w,
2952w, 2929w, 2891w, 2857w, 1661m, 1472w, 1463w, 1441w, 1389w, 1361w, 1254m, 1214w, 1154m, 1103s, 1078m,
1029s, 964m, 919m, 893m, 864m, 834vs, 776s. 1H-NMR (300 MHz, CDCl3): see Table 5; additionally, 5.04 (d, J ˆ
6.5), 4.83( d, J ˆ 6.5), 4.82 (d, J ˆ 6.5), 4.76 (d, J ˆ 6.5) (2 MeOCH2); 4.37 (br. s, exchanged with D2O, NH2);
3.47, 3.41 (2s, 2 MeO); 0.87 (s, Me3C); 0.10, 0.09 (2s, Me2Si). 13C NMR (CDCl3): see Table 5; additionally, 97.46,
97.30 (2t, 2 MeOCH2); 56.41, 56.23(2 q, 2 MeO); 25.81 (q, Me3C); 18.08 (s, Me3C); À 4.56, À 4.77 (2q, Me2Si).
‡
‡
HR-MALDI-MS: 387.1927 (100, [M ‡ Na] ; C15H32N2NaO6Si ; calc. 387.1922). Anal. calc. for C15H32N2O6Si
(364.51): C 49.43, H 8.85, N 7.69; found: C 49.65, H 8.86, N 7.60.
6-O-[(tert-Butyl)dimethylsilyl]-2,3-O-isopropylidene-5-O-(methylsulfonyl)-d-mannono-1,4-lactone (53).
A cooled (08) soln. of 52 [87] (550 mg, 1.66 mmol) in CH2Cl2 (2 ml) and pyridine (1 ml) was treated with
MsCl (194 ml, 2.5 mmol), stirred at 08 for 1 h and at 238 for 12 h, treated with H2O (10 ml), and extracted with
CH2Cl2 (3 Â 20 ml). The combined org. layers were dried and evaporated. FC (CH2Cl2) gave 53 (545 mg, 80%).
White crystals. M.p. 119 1208 (CH2Cl2). Rf (cyclohexane/AcOEt 2 :1) 0.41. [a]2D5 ˆ ‡17.0 (c ˆ 1.0, CHCl3). IR
(CHCl3): 3031w, 2992w, 2956m, 2931m, 2888w, 2858w, 1799s, 1473w, 1463w, 1376m, 1364s, 1259m, 1219m, 1176s,
1155m, 1111s, 1026m, 970m, 959m, 926s, 83 8s. 1H-NMR (300 MHz, CDCl3): 4.94 4.84 (m, HÀC(2), HÀC(3),
HÀC(5)); 4.77 (dd, J ˆ 8.1, 2.5, HÀC(4)); 4.14 (dd, J ˆ 12.1, 2.2, HÀC(6)); 3.93 (dd, J ˆ 12.1, 3.7, H'ÀC(6)); 3.10
(s, MsO); 1.49, 1.41 (2s, Me2C); 0.90 (s, Me3C); 0.10, 0.09 (2s, Me2Si). 13C-NMR (75 MHz, CDCl3): 172.75 (s,
CˆO); 114.65 (s, Me2C); 79.05 (d, C(2)); 76.07, 75.64, 74.82 (3d, C(3), C(4), C(5)); 62.28 (t, C(6)); 37.92 (q,
MsO); 27.09, 26.22 (2q, Me2C); 26.07 (q, Me3C); 18.60 (s, Me3C); À 5.14, À 5.21 (2q, Me2Si). HR-MALDI-MS:
‡
‡
433.1325 (100, [M ‡ Na] , C16H30NaO8SSi ; calc. 433.1329). Anal. calc. for C16H30O8SSi (410.56): C 46.81, H
7.36, S 7.81; found: C 46.91, H 7.30, S 7.74.
5,6-Bis-O-[(tert-butyl)dimethylsilyl]-4-deoxy-4-hydrazino-2,3-O-isopropylidene-l-allono-1,4-lactam (55).
1) A suspension of 53 (500 mg, 1.22 mmol) in NH2NH2 ¥ H2O (3ml) was stirred at 23 8 for 14 h and at 608 for
3h. Co-evaporation with toluene and FC (CH 2Cl2/MeOH/Et3N 95 :5 :3) gave 6-O-[(tert-butyl)dimethylsilyl]-4-
deoxy-4-hydrazino-2,3-O-isopropylidene-l-allono-1,4-lactam (54; 409 mg, 97%). White solid. Rf (cyclohexane/
AcOEt 1:2) 0.27. [a]D25 ˆ ‡46.3( c ˆ 0.7, CHCl3). IR (neat): 3327w (br.), 2953m, 2929w, 2857w, 1689s, 1621w,
1472w, 1463w, 1382w, 1374m, 1252m, 1211m, 1155m, 1117m, 1094s, 1050m, 998m, 93 6w, 902w, 873m, 833vs, 812s,
806s, 775vs. 1H-NMR (300 MHz, CDCl3): 4.67 (d, J ˆ 6.2, HÀC(2)); 4.54 (d, J ˆ 6.2, HÀC(3)); 4.24 (br. s,
exchanged with D2O, NH2); 4.12 (br. t, J ˆ 6.6, HÀC(5)); 3.82 3.63 (m, HÀC(4), 2 HÀC(6)); 1.38, 1.30 (2s,
Me2C); 0.88 (s, Me3C); 0.07 (s, Me2Si). 13C-NMR (75 MHz, CDCl3): 170.82 (s, CˆO); 111.67 (s, Me2C); 76.57 (d,
C(2)); 72.57 (d, C(3)); 67.57, 67.50 (2d, C(4), C(5)); 64.00 (t, C(6)); 27.08, 25.44 (2q, Me2C); 26.11 (q, Me3C);
18.51 (s, Me3C); À 5.15, À 5.20 (2q, Me2Si).
2) A soln. of 54 (520 mg, 1.5 mmol) in CH2Cl2 (5 ml) and pyridine (1 ml) was treated with TBSOTf
(0.69 ml, 3.0 mmol), stirred at 08 for 1 h and at 238 for 24 h, treated with H2O (10 ml), and extracted with
CH2Cl2 (3 Â 20 ml). The combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt 4 :1) gave
55 (654 mg, 95%). White crystals. M.p. 66 688 (cyclohexane/AcOEt). Rf (cyclohexane/AcOEt 1:2) 0.80.
[a]2D5 ˆ ‡64.8 (c ˆ 0.37, CHCl3). IR (neat): 3322w, 3280w, 3211w, 2989w, 2953m, 2929m, 2885w, 2857w, 1718s,
1629w, 1471w, 1462w, 1428w, 1376w, 1368w, 1361w, 1255m, 1230m, 1116s, 1084s, 1051w, 1001m, 93 7w, 916m,
891m, 831vs, 806s, 773vs. 1H-NMR (500 MHz, CDCl3): 4.71 (d, J ˆ 6.2, HÀC(2)); 4.54 (d, J ˆ 6.2, HÀC(3)); 4.11
(ddd, J ˆ 7.3, 4.8, 1.3, HÀC(5)); 3.94 (s, NH2); 3.82 (d, J ˆ 1.2, HÀC(4)); 3.69 (dd, J ˆ 10.5, 4.8, HÀC(6)); 3.66
(dd, J ˆ 10.5, 7.2, H'ÀC(6)); 1.41, 1.34 (2s, Me2C); 0.90, 0.82 (2s, 2 Me3C); 0.074, 0.073, 0.047, À 0.039 (4s,
2 Me2Si). 13C-NMR (125 MHz, CDCl3): 169.45 (s, CˆO); 111.52 (s, Me2C); 76.36 (d, C(2)); 72.21 (d, C(3));
68.98, 66.93(2 d, C(4), C(5)); 64.21 (t, C(6)); 26.97, 25.31 (2q, Me2C); 25.82, 25.68 (2q, 2 Me3C); 18.20, 17.69 (2s,
‡
‡
2 Me3C); À 4.75, À 4.83, À 5.51, À 5.55 (4q, 2 Me2Si). MALDI-MS: 483(11, [ M ‡ Na] ), 461 (26, [M ‡ H] ).
Anal. calc. for C21H44N2O5Si2 (460.76): C 54.74, H 9.62, N 6.08; found: C 54.85, H 9.49, N 5.98.
2l-(2,3/4)-4-O-[(tert-Butyl)dimethylsilyl]-5-diazo-2,3-O-isopropylidene-2,3,4-trihydroxycyclopentanone
(56). A soln. of 41 (95 mg, 0.3mmol) in toluene (2 ml) was treated with a suspension of Pb(OAc) 4 (400 mg,
0.9 mmol) in toluene (2 ml), stirred at r.t. for 1 h, treated with H2O, and extracted with Et2O (3 Â 30 ml). The
combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt 12 :1 ! 6 :1) gave 56 (35 mg, 37%).
Yellow crystals. M.p. 69 718 (hexane). Rf (hexane/AcOEt 4 :1) 0.50. [a]2D5 ˆ ‡72.7 (c ˆ 0.8, CHCl3). UV
(MeOH): 294 (3.38), 253 (4.01). IR (CHCl3): 3026w, 2994w, 2955m, 2932m, 2859w, 2100s, 1683s, 1471w, 1463w,
1385w, 1376m, 1354m, 1334m, 1313w, 1289m, 1261m, 1154w, 1084s, 1004w, 926w, 83 9s. 1H-NMR (300 MHz,
CDCl3): see Table 3; additionally, 1.42, 1.36 (2s, Me2C); 0.91 (s, Me3C); 0.17, 0.13(2 s, Me2Si). 13C-NMR
(75 MHz, CDCl3): see Table 3; additionally, 113.19 (s, Me2C); 27.52 (q, MeC); 25.81 (q, Me3C, MeC); 18.21 (s,

2430
Helvetica Chimica Acta Vol. 87 (2004)
‡
‡
Me3C); À 4.45, À 4.59 (2q, Me2Si). ESI-MS: 647 (72, [2M ‡ Na] ); 367 (80, [M ‡ MeOH ‡ Na] ); 351 (100,
‡
‡
‡
[M ‡ K] ); 335 (65, [M ‡ Na] ); 313 (25, [M ‡ H] ). Anal. calc. for C14H24N2O4Si (312.44): C 53.82, H 7.74, N
8.97; found: C 53.97, H 7.55, N 8.78.
Crystal Structure of 56. Recrystallization of 56 in hexane gave crystals suitable for X-ray analysis,
C14H24N2O4Si (312.44); monoclinic P21; a ˆ 7.3727 (3) ä, b ˆ 9.7904 (4) ä, c ˆ 13.0287 (6) ä, b ˆ 104.695 (2)8;
Vˆ 909.67 (7) ä3; Dcalc. ˆ 1.141 Mg/m3; Z ˆ 2. From a crystal of size 0.24  0.2  0.04 mm, 3743 reflections were
measured on an KappyCCD diffractometer with MoKa radiation (graphite monochromator, l ˆ 0.71073ä) at
293K. R ˆ 0.0661, Rw ˆ 0.1583.
2l-(2/3,4)-4-O-[(tert-Butyl)dimethylsilyl]-5-diazo-2,3-bis-O-(methoxymethyl)-2,3,4-trihydroxycyclopenta-
none (57). A soln. of 46 (36 mg, 0.1 mmol) in toluene (1 ml) was treated with a suspension of Pb(OAc)4
(133 mg, 0.3 mmol) in toluene (2.5 ml), stirred at r.t. for 1 h, treated with H2O, and extracted with Et2O (3 Â
5 ml). The combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt 16 :1 ! 4 :1) gave 57
(8 mg, 22%). Pale yellow syrup. Rf (cyclohexane/AcOEt 2 :1) 0.50. [a]2D5 ˆ À140.7 (c ˆ 0.5, CHCl3). UV
(MeOH): 294 (3.15), 254 (3.87). IR (CHCl3): 2956m, 2932m, 2897m, 2859m, 2827w, 2097s, 1692s, 1472w, 1456m,
1317s, 1255m, 1210m, 1153s, 1124s, 1090m, 1043s, 1015s, 83 3s. 1H-NMR (300 MHz, CDCl3): see Table 3;
additionally, 5.01, 4.81 (2d, J ˆ 6.5, MeOCH2); 4.75 (s, MeOCH2); 3.46, 3.42 (2s, 2 MeO); 0.91 (s, Me3C); 0.12,
0.10 (2s, Me2Si). 13C-NMR (75 MHz, CDCl3): see Table 3; additionally, 96.38, 94.90 (2t, 2 MeOCH2); 55.96,
‡
55.83(2 q, 2 MeO); 25.72 (q, Me3C); 18.21 (s, Me3C); À 4.08, À 4.61 (2q, Me2Si). ESI-MS: 399 (34, [M ‡ K] ),
‡
‡
383 (100, [M ‡ Na] ), 355 (80, [M ‡ Na À N2] ). Anal. calc. for C15H28N2O6Si (360.48): C 49.98, H 7.83, N 7.77;
found: C 50.10, H 7.95, N 7.60.
2d-(2,4/3)-4-O-[(tert-Butyl)dimethylsilyl]-5-diazo-2,3-bis-O-(methoxymethyl)-2,3,4-trihydroxycyclopenta-
none (58). A soln. of 51 (36 mg, 0.1 mmol) in toluene (1 ml) was treated with a suspension of Pb(OAc)4
(400 mg, 0.9 mmol) in toluene (3ml), stirred at r.t. for 1 h, treated with H 2O, and extracted with Et2O (3 Â
5 ml). The combined org. layers were dried and evaporated. FC (cyclohexane/AcOEt 16 :1 ! 8 :1) gave 58
(9 mg, 25%). Yellow syrup. Rf (cyclohexane/AcOEt 2 :1) 0.58. [a]2D5 ˆ ‡103.3 (c ˆ 0.5, CHCl3). UV (MeOH):
294 (3.22), 258 (3.85). IR (CHCl3): 3012w, 2956m, 2932m, 2898w, 2859w, 2827w, 2098s, 1686s, 1472w, 1464w,
1318s, 1261m, 1153s, 1110s, 1078m, 1034s, 1004m, 919w, 844s. 1H-NMR (300 MHz, CDCl3): see Table 3;
additionally, 5.06, 4.83, 4.78, 4.77 (4d, J ˆ 6.5, 2 MeOCH2); 3.45, 3.43 (2s, 2 MeO); 0.91 (s, Me3C); 0.17, 0.12 (2s,
Me2Si). 13C-NMR (75 MHz, CDCl3): see Table 3; additionally, 96.70, 96.47 (2t, MeOCH2); 56.31 (q, 2 MeO);
‡
‡
25.74 (q, Me3C); 18.10 (s, Me3C); À 4.16, À 4.43(2 q, Me2Si). ESI-MS: 743(9, [2 M ‡ K] ), 399 (42, [M ‡ K] ),
‡
‡
383 (100, [M ‡ Na] ), 355 (93, [M À N2 ‡ Na] ).
4-Amino-5,6-bis-O-[(tert-butyl)dimethylsilyl]-4-deoxy-4a-[(dimethylsulfinylidene)amino]-2,3-O-isopropy-
lidene-l-allono-1,4-lactam (59). A soln. of 55 (230 mg, 0.5 mmol) in toluene (10 ml) was added dropwise to a
cooled (08) suspension of Pb(OAc)4 (665 mg, 1.5 mmol) in toluene (10 ml) and DMSO (2 ml). The mixture was
stirred for 2 h at 08, treated with H2O (10 ml), and extracted with Et2O (3 Â 30 ml). The combined org. layers
were dried (MgSO4) and evaporated. FC (cyclohexane/AcOEt 1:2) gave 59 (144 mg, 54%). White crystals. M.p.
152 1548 (hexane/Et2O). Rf (cyclohexane/AcOEt 1:2) 0.10. [a]2D4 ˆ À4.5 (c ˆ 0.5, CHCl3). IR (CHCl3): 3018s,
2956m, 2931m, 2858m, 1694s, 1471w, 1462w, 1410w, 1383w, 1374m, 1256m, 1154w, 1118m, 1088s, 1045m, 1021m,
937w, 83 9s, 814w. 1H-NMR (300 MHz, CDCl3): 4.77 (d, J ˆ 6.2, HÀC(2)); 4.53( d, J ˆ 6.2, HÀC(3)); 4.29 (t, J ꢀ
5.3, HÀC(5)); 3.98 (s, HÀC(4)); 3.75 3.62 (m, 2 HÀC(6)); 3.20, 3.14 (2s, Me2SˆO); 1.47, 1.35 (2s, Me2C); 0.90,
0.84 (2s, 2 Me3C); 0.07, 0.02 (2s, 2 Me2Si). 13C-NMR (75 MHz, CDCl3): 169.42 (s, CˆO); 111.00 (s, Me2C); 76.33
(d, C(2)); 72.68 (d, C(3)); 69.33, 68.40 (2d, C(4), C(5)); 64.69 (t, C(6)); 40.83, 40.14 (2q, Me2SˆO); 27.45, 25.38
(2q, Me2C); 25.91 (q, 2 Me3C); 18.28, 17.89 (2s, 2 Me3C); À 4.40, À 4.82, À 5.31, À 5.39 (4q, 2 Me2Si). MALDI-
‡
MS: 559 (8.5, [M ‡ Na] ), 353 (100). Anal. calc. for C23H48N2O6SSi2 (536.88): C 51.46, H 9.01, N 5.22, S 5.97;
found: C 51.56, H 8.84, N 5.06, S 6.09.
Crystal Structure of 59. Recrystallization of 59 in hexane/Et2O gave crystals suitable for X-ray analysis:
C23H48N2O6SSi2 (536.88): orthorhombic P212121; a ˆ 8.10130 (10) ä, b ˆ 9.00780 (10) ä, c ˆ 42.9596 (6) ä, b ˆ
908; Vˆ 3134.97 (8) ä3; Dcalc. ˆ 1.138 Mg/m3; Z ˆ 4. From a crystal of size 0.24  0.2  0.1 mm, 6850 reflections
were measured on an KappyCCD diffractometer with MoKa radiation (graphite monochromator, l ˆ
0.71073ä) at 298 K. R ˆ 0.1766, Rw ˆ 0.2822.

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Received April 24, 2004