Convenient access to both enantiomers of new azido- and aminoinositols via a chemoenzymatic route

Article abstract of DOI:10.1016/S0957-4166(98)00271-7

1,2-diacetylconduritol E, (±)-1, through complementary use of Mucor miehei (Lipozyme IM) and Candida cylindracea lipases, affords (1S)-1,2- diacetylconduritol E, (+)-1, (1R)-1,2-diacetylconduritol E, (-)-1, (1S)- 1,2,4-triacetylconduritol E, (+)-2, (1R)-1

Full text of DOI:10.1016/S0957-4166(98)00271-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 2809–2817
Convenient access to both enantiomers of new azido- and
aminoinositols via a chemoenzymatic route
Claudia Sanfilippo, Angela Patti, Mario Piattelli and Giovanni Nicolosi ∗
Istituto CNR Studio Sostanze Naturali di Interesse Alimentare e Chimico-Farmaceutico, Via del Santuario 110,
I-95028 Valverde CT, Italy
Received 28 May 1998; accepted 7 July 1998
Abstract
1,2-diacetylconduritol E, (ꢀ)-1, through complementary use of Mucor miehei (Lipozyme® IM) and Candida
cylindracea lipases, affords (1S)-1,2-diacetylconduritol E, (+)-1, (1R)-1,2-diacetylconduritol E, (−)-1, (1S)-1,2,4-
triacetylconduritol E, (+)-2, (1R)-1,2,4-triacetylconduritol E, (−)-2, with high enantiomeric excesses and chemical
yields. Following two different methods, diester (+)-1 has been transformed into azidoinositol (−)-4 to give 1L-
4-amino-4-deoxy-chiro-inositol, whereas triester (−)-2 furnished the azidoinositol (+)-13, easily converted into
1L-4-amino-4-deoxy-myo-inositol. © 1998 Published by Elsevier Science Ltd. All rights reserved.
1. Introduction
The recent discovery that D-myo-inositol 1,4,5-tris(phosphate) is involved in signal transduction in
animal cells has caused an increasing interest in inositol analogues. In particular, azido- and amino
derivatives have great potential as bioactive molecules, since the direct antiproliferative activity on
tumoral cells (fibroblasts) of azido myo-inositols has been well-recognised,1 while the enzyme inhibitory
activity of glycosidases reported for free and conjugated aminoinositols plays a central role in antibiotic
action.2
The presence in the framework of these cyclitols of six stereogenic carbons makes their synthesis
in enantiopure form very demanding and only a few examples have been reported as yet. myo-Inositol
derivatives have been prepared starting from chiral L-quebrachitol3 or D-glucose,4 and aminoinositols
with the allo-configuration have been obtained by stereoselective addition of chiral nitroso-dienophiles
to cis-1,2-diacetoxycyclohexa-3,5-diene.5
Chiral conduritols are promising starting materials for the synthesis of azido- and aminoinositols, since
they contain four stereogenic centres of defined configuration and a double bond suitable to introduce two
∗
Corresponding author. E-mail: nicolosi@issn.ct.cnr.it
0957-4166/98/$ - see front matter © 1998 Published by Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00271-7

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additional ones. Moreover, selective protection of all but one of the hydroxyl groups can be used for the
conversion of the free OH group into a nitrogenous substituent or the generation of discriminatory effects
at vinylic positions.
In this paper we wish to describe the preparation of the previously unreported enantiomers of both
4-amino-4-deoxy-chiro-inositol and 4-amino-4-deoxy-myo-inositol, starting from conduritol E diacetate,
(ꢀ)-1 and using biocatalytic procedures paired with stereospecific reactions.
2. Results and discussion
2.1. Preparation of enantiopure (−)-1 and (+)-2
Resolution of (ꢀ)-1 by esterification with vinyl acetate in tert-butyl methyl ether promoted by
immobilised lipase from Mucor miehei (Lipozyme® IM) has been described in a previous paper.6 This
reaction led to the preparation of triacetate (−)-2 and unreacted diacetate (+)-1 with high chemical yields
and enantiomeric excesses. At the onset of the present work aimed at the synthesis of new aminocyclitols
we intended to prepare both enantioforms of these partial esters and therefore we screened several
lipases in search of one possessing the opposite stereopreference to that of M. miehei. Among the
lipases used, only Candida cylindracea lipase had the desired (S)-stereopreference, but unfortunately
its enantioselectivity was low (E=20) and a preparative run afforded (+)-2 and (−)-1 with unsatisfactory
e.e.7 Therefore, we resorted to a different approach exploiting the opposite stereopreferences of M. miehei
and C. cylindracea lipases in complementary transesterification reactions (Scheme 1).
Scheme 1.
In a first step, racemic (ꢀ)-1 was subjected to kinetic resolution by esterification catalysed by M. miehei
lipase. Following chromatographic separation, triester (−)-2 was subjected to regioselective alcoholysis
by reaction with n-butanol in the presence of Lipozyme® IM to afford after 4 h (−)-1 in 55% yield and

C. Sanfilippo et al. / Tetrahedron: Asymmetry 9 (1998) 2809–2817
2811
e.e.>95%. The amount of (−)-1 did not increase by prolonging the reaction time and products of further
deacylation began to form.8
Conversely, (+)-2 with e.e.>95% was obtained by treatment of (+)-1 with vinyl acetate in the presence
of C. cylindracea. The hydroxyl group at C-2 did not suffer esterification even after prolonged reaction
times, possibly due to steric hindrance, so that the desired triester was in any case the only product.
2.2. Synthesis of new aminoinositols
Enantiopure (+)-1 and (−)-2 have been transformed into three new aminoinositols following two
different methodologies. In the first one, diester (+)-1 was converted into amino-chiro-inositol (−)-7
through stereoselective epoxidation followed by regioselective nucleophilic ring opening (Scheme 2).
Scheme 2.
Since diester (+)-1 lacks the C2-symmetry of the parent tetrol, two diastereoisomeric epoxides could
be expected by epoxidation from the double bond. As a matter of fact, reaction of (+)-1 with m-CPBA
afforded a single product, (+)-3, whose structure, anticipated by taking into consideration the reported
syn-orientation effect of hydroxyl groups,9 was subsequently confirmed by the stereochemical outcome
of the following ring opening reaction. Treatment of (+)-3 with NaN3 yielded the partially protected
azidoinositol (−)-4 as a single product, whose catalytic hydrogenation (Pd/C) gave the corresponding
aminoderivative (−)-5. In the 1H NMR spectrum of the latter, a distinct resonance at δ 3.42 was present,
assigned by heteronuclear correlation to the proton at C-4. Selective decoupling of H-4 showed−that the
amino group is not adjacent to the ester groups, thus indicating a regioselective attack of the N3 on the
less hindered position of epoxyderivative (+)-3. The stereoselectivity observed in the nucleophilic ring
opening of (+)-3, higher than that reported for the underivatised conduritol E epoxide,10 is probably due
to loss of C2-symmetry following the introduction of acetoxy groups. Definite assignment of structure
(−)-5 was possible by its transformation into peracetate (+)-6, whose 1H NMR spectrum showed distinct
resonances for each methine proton. Complete analysis of all the observed coupling constants and in
particular the large values of JH3−H4 and JH4−H5, indicating the trans–trans diaxial orientation of the
three protons in question, allowed compound (+)-6 to be assigned the same stereochemistry as L-chiro-
inositol.
Reaction of (−)-5 with aqueous NH4OH furnished quantitatively 1L-4-amino-4-deoxy-chiro-inositol,
isolated as the salt with acetic acid, (−)-7. Following the same procedure, 1D-4-amino-4-deoxy-chiro-
inositol can be prepared starting from (−)-1.
In the second method, triester (−)-2 was profitably used in the preparation of other aminoinositol
derivatives. By conventional tosylation it gave (−)-8, which has a trans relationship between the tosyloxy
and a vicinal acetyloxy group, the appropriate requirement to give an intramolecular displacement.11
Thus, treatment of (−)-8 with KOH in MeOH (Scheme 3) afforded quantitatively epoxide (−)-9, in turn
converted into acetate (−)-10 to avoid possible epoxide migration, a reaction reported for α,β-epoxy
alcohols.12 Treatment of (−)-10 with NaN3 in the presence of NH4Cl and subsequent hydrolysis with

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aqueous NH4OH gave two diastereoisomeric azides in a 9:1 ratio, as shown by 1H NMR analysis of the
crude product.13
Scheme 3.
After purification by column chromatography, the major azide, (−)-11, was assigned the structure of 2-
azidoconduritol B from its magnetic resonance properties. Its 1H NMR spectrum contains a broad singlet
due to the olefinic protons, typical of the conduritol B series,14 and in addition two partially superimposed
double doublets for H-2 and H-3, whose coupling constants confirmed the all-trans orientation of H-1–H-
4.
Azidoconduritol (−)-11 by reaction with N-methylmorpholine oxide (NMMO) in the presence of
catalytic amounts of OsO4 in 48 h yielded two products of cis-dihydroxylation, which were isolated by
column chromatography and further purified as the acetates 12 and (+)-13, obtained in a ratio of 4:6. Lack
of optical activity and simplification of the 1H NMR spectrum of 12 revealed its meso-nature and allowed
the structure of 5-azido-5-deoxy-myo-inositol pentaacetate to be assigned. Conversely, the presence of
five distinct singlets for CH3CO groups in the 1H NMR spectrum of (+)-13 confirmed its structure of 1L-
4-azido-4-deoxy-myo-inositol. Each azido inositol was then reduced with Pd/C and hydrolysed to give
respectively amino derivatives 14 and (−)-15, isolated as salts with acetic acid (Scheme 4). Following
the same procedure, the amino derivative (+)-15 can be synthesised starting from triester (+)-2.
Scheme 4.

C. Sanfilippo et al. / Tetrahedron: Asymmetry 9 (1998) 2809–2817
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3. Conclusion
The data obtained show that the complementary use of Mucor miehei and Candida cylindracea
lipases, possessing opposite stereoreferences, allows access to both enantiomers of 1,2-diacetyl- and
1,2,4-triacetylconduritol E with high optical and chemical yield. Due to their structural features, these
esters can be utilised as key intermediates in the synthesis of compounds of a more complex structure.
In our laboratory, 1,2-diacetylconduritol E, (+)-1, has been transformed into 1L-4-amino-4-deoxy-chiro-
inositol, (−)-7 and 1,2,4-triacetylconduritol E, (−)-2 has furnished 1L-4-amino-4-deoxy-myo-inositol,
(−)-15, all in good overall yield. Furthermore, the described syntheses also allow chiral epoxy- or azido-
derivatives to be obtained which could themselves be bioactive molecules and starting materials for the
preparation of other enantiopure cyclitols.
4. Experimental section
1H and 13C NMR spectra were recorded at 250.13 and 62.9 MHz respectively. Chemical shifts (δ) are
reported in ppm relative to TMS in the solvent specified; all coupling constants (J) are in hertz. Optical
rotations were measured on a DIP 135 JASCO instrument. GC analyses were performed on HP-5 (5%
phenylmethylsilicone) or Chiraldex G-DA (dialkyl γ-cyclodextrin) capillary column on a Perkin–Elmer
8500 instrument. Melting points were determined on a MELT-TEMP II, Lab. device and are uncorrected.
All chemicals were purchased from Aldrich or Fluka. Lipases from Candida cylindracea and Pseu-
domonas cepacia were obtained from Amano International Enzyme Co. Porcine pancreas lipase was
from Sigma. Lipozyme® IM (immobilised lipase from Mucor miehei) and Novozym® 435 (immo-
bilised lipase from Candida antarctica) are registered marks from Novo Nordisk. Conduritols (+)-1
and (−)-2 were available from previous work.6 Column chromatography was performed on silica gel
or LiChroprep® DIOL 40–63 µm (Merck); analytical TLC was carried out on Merck silica gel 60-F254
precoated glass plates and compounds were visualised by spraying with molybdophosphoric acid.
4.1. General procedure for small-scale esterification of 1,2-dihydroxy-3,5-diacetyloxycyclohex-5-ene
(ꢀ)-1
Lipase (20 mg/ml) was added to a solution of (ꢀ)-1 (10 mg/ml) in t-BME containing vinyl acetate
(30 µl/ml) and the suspension was shaken at 40°C. The progress of the reaction was monitored by
GC analysis of aliquots, injected after acylation with propionic anhydride/pyridine. The reaction was
then stopped, the enzyme filtered off and the filtrate taken to dryness. After work-up of the reaction
mixture on the Si-DIOL column, the enantiomeric excess of triester 2 was determined by chiral GC after
conventional acetylation. The stereochemistry of 2 was assessed from its known optical properties.6
4.2. Kinetic resolution of (ꢀ)-1 with Candida cylindracea lipase
Lipase from C. cylindracea (600 mg) and vinyl acetate (0.3 ml, 3.2 mmol) were added to a solution of
(ꢀ)-1 (300 mg, 1.3 mmol) in t-BME (30 ml). The suspension was maintained at 45°C under continuous
stirring until conversion of the substrate reached 49% (30 h). The reaction mixture was then filtered and
the solution taken to dryness. The residue was then subjected to column chromatography on Si-DIOL
(hexane:EtOAc=7:3) to give (+)-2 with 80% e.e. and unreacted (−)-1 with 77% e.e.

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4.3. (1R,2R,3S,4R)-1,2-Dihydroxy-3,4-diacetyloxycyclohex-5-ene (−)-1
Lipozyme (200 mg) and n-BuOH (0.033 ml, 0.36 mmol) were added to a solution of (−)-2 (100 mg,
0.36 mmol, e.e.>95%) in t-BME (10 ml). The reaction was monitored by GC analysis and after 4 h (−)-1
was isolated by column chromatography (hexane:EtOAc=1:1), yield 55%, [α]D −213.2 (c 1.2, CHCl3).
4.4. (1S,2S,3R,4S)-2-Hydroxy-1,3,4-triacetyloxycyclohex-5-ene (+)-2
Lipase from C. cylindracea (140 mg) and vinyl acetate (0.033 ml, 0.36 mmol) were added to a solution
of (+)-1 (70 mg, 0.30 mmol, e.e.>95%) in t-BME (7 ml). After 24 h, conversion was complete (TLC)
and (+)-2 was crystallised from EtOAc:hexane (73 mg, 89% yield); [α]D +275.8 (c 1.2, CHCl3).
4.5. (1R,2S,3R,4S,5R,6R)-1,2-Dihydroxy-3,4-diacetyloxy-5,6-epoxycyclohexane (+)-3
3-Chloroperoxybenzoic acid (650 mg, 3.76 mmol) was added to a solution of (+)-1 (420 mg, 1.82
mmol, e.e.>95%) in CH2Cl2 (20 ml) and the mixture kept at room temperature for 48 h. After evaporation
of the solvent, the residue was subjected to column chromatography (EtOAc:hexane=1:1) to give (+)-3
(385 mg, 86% yield); [α]D +104.6 (c 1.2, CHCl3); 1H NMR (CDCl3) δ 2.06 (3H, s), 2.11 (3H, s), 3.38
(1H, dd, J=3.3 and 2.2), 3.52 (1H, dd, J=3.6 and 3.3), 3.90 (1H, dd, J=9.3 and 5.2), 4.32 (1H, dd, J=5.2
and 3.6), 5.13 (1H, dd, J=9.3 and 3.5), 5.65 (1H, dd, J=3.5 and 2.2); 13C NMR (CDCl3) δ 20.6, 20.7,
54.1, 54.7, 65.4, 66.6, 66.7, 68.3, 169.7, 170.5.
4.6. 1L-1,2-Diacetoxy-4-azido-4-deoxy-chiro-inositol (−)-4
NaN3 (154 mg, 2.36 mmol) and NH4Cl (126 mg, 2.35 mmol) were added to a solution of epoxide (+)-3
(345 mg, 1.40 mmol) in DMF (8 ml). The suspension was stirred for 36 h at 50°C and then filtered. The
filtrate was taken to dryness and the residue purified on Si gel (EtOAc:hexane=3:2) to give azidoinositol
(−)-4 (323 mg, 79% yield); [α]D −37.2 (c 0.5, CHCl3); 1H NMR (CD3OD) δ 2.04 (3H, s), 2.09 (3H, s),
3.64 (3H, m), 3.89 (1H, m), 5.18 (1H, m), 5.31 (1H, m); 13C NMR (CD3OD) δ 20.7, 20.9, 67.9, 70.8,
71.0, 71.2, 71.8, 73.0, 171.3, 172.0. Anal. calcd for C10H15N3O7: C, 41.52; H, 5.23; N, 14.53. Found: C,
41.58; H, 5.29; N, 14.47.
4.7. 1L-1,2-Diacetoxy-4-amino-4-deoxy-chiro-inositol (−)-5
Azido compound (−)-4 (300 mg, 1.02 mmol) in EtOH (8 ml) was hydrogenated in the presence of Pd/C
(20 mg) at barometric pressure and room temperature. After 24 h, the reaction mixture was centrifuged
and filtered and the supernatant taken to dryness to give (−)-5 (263 mg, 98% yield); [α]D −20.8 (c 0.4,
EtOH); 1H NMR (D2O): δ 2.10 (3H, s), 2.15 (3H, s), 3.42 (1H, t, J=10.6), 4.06 (3H, m), 5.11 (1H, dd,
J=10.0 and 3.1), 5.36 (1H, t, J=3.1); 13C NMR (CD3OD) δ 20.6, 20.7, 56.4, 68.5, 68.9, 70.6, 71.7, 73.4,
171.1, 171.9.
4.8. 1L-4-Amino-4-deoxy-chiro-inositole-hexaacetate (+)-6
An aliquot of (−)-5 was subjected to conventional acetylation (Ac2O/py) to give (+)-6; [α]D +13.7 (c
0.3, C6H6); 1H NMR (C6D6) δ 1.46 (3H, s), 1.59 (3H, s), 1.65 (3H, s), 1.72 (3H, s), 1.75 (6H, s), 4.71
(1H, d, J=9.9), 5.06 (1H, ddd, J=11.2, 10.3 and 9.9), 5.32 (1H, dd, J=11.2 and 2.8), 5.50 (1H, t, J=10.3),

C. Sanfilippo et al. / Tetrahedron: Asymmetry 9 (1998) 2809–2817
2815
5.68 (1H, dd, J=4.0 and 2.8), 5.73 (2H, m); 13C NMR (C6D6) δ 20.4, 20.6, 20.9, 23.5, 50.8, 68.4, 68.7,
70.2, 70.6, 71.3, 169.3, 169.7, 170.1, 170.8, 171.1.
4.9. 1L-4-Ammonium-4-deoxy-chiro-inositole acetate (−)-7
Deacetylation of (−)-5 with MeOH:NH4OH (9:1) gave (−)-7, [α]D −28.7 (c 0.7, MeOH); 1H NMR
(CD3OD) δ 2.04 (3H, s), 3.58 (1H, t, J=10.0), 3.77 (2H, m), 3.96 (2H, m), 4.05 (1H, t, J=10.0); 13C
NMR (CD3OD) δ 22.9, 55.4, 71.2, 72.7, 72.9, 73.3, 73.5, 174.7.
4.10. (1R,2R,3R,4R)-1,3,4-Triacetyloxy-2-tosyloxycyclohex-5-ene (−)-8
Pyridine (0.4 ml, 4.97 mmol) and p-toluensulfonyl chloride (900 mg, 4.72 mmol) were added to a
solution of (−)-2 (600 mg, 2.20 mmol, e.e.>95%) in CH2Cl2 (25 ml) and the mixture was stirred at
35°C overnight. After washing with H2O, the organic layer was dried over Na2SO3 and the solvent
removed under reduced pressure. The residue was purified by column chromatography over Si gel
(hexane:EtOAc=8:2) and finally recrystallised from MeOH to give (−)-8 (883 mg, 94%): mp 99–100°C;
[α]D −183.2 (c 2.0, CHCl3); 1H NMR (CDCl3) δ 1.91 (3H, s), 2.00 (3H, s), 2.04 (3H, s), 2.46 (3H, s)
5.06 (1H, dd, J=9.7 and 4.3), 5.35 (1H, dd, J=9.7 and 4.0), 5.58 (1H, dd, J=4.3 and 4.0), 5.64 (1H, dd,
J=4.0 and 4.3), 5.86 (1H, dd, J=10.0 and 4.0), 5.94 (1H, dd, J=10.0 and 4.3), 7.36 (2H, d, J=8.3), 7.82
(2H, d, J=8.3); 13C NMR (CDCl3) δ 20.4, 20.6, 21.6, 66.0, 66.3, 66.5, 73.5, 127.9, 129.8, 133.5, 145.2,
169.6, 169.8.
4.11. (1R,2R,3S,4R)-1,4-Diacetyloxy-2,3-epoxycyclohex-5-ene (−)-10
Aqueous KOH was added dropwise to an icy solution of compound (−)-8 (700 mg, 1.64 mmol)
in MeOH (35 ml). After 30 min, the reaction was kept under stirring for 2 h at room temperature.
After addition of ethyl acetate, the precipitate of potassium tosylate was filtered off and the filtrate
was evaporated under reduced pressure to leave a residue that was subjected to conventional acetylation
(Ac2O/py) to afford (−)-10. Recrystallised from EtOAc:hexane (291 mg, 84% yield) it had mp 86–87°C,
[α]D −157.3 (c 1.4, CHCl3); 1H NMR (CDCl3) δ 2.11 (3H, s), 2.19 (3H, s), 3.44 (1H, m), 3.62 (1H, m),
5.56 (1H, m), 5.72 (2H, m), 5.84 (1H, m); 13C NMR (CDCl3) δ 20.7, 20.9, 50.9, 51.8, 63.9, 66.8, 124.0,
127.0, 169.9, 170.4.
4.12. (1R,2R,3S,4R)-1,2,4-Trihydroxy-3-azido-cyclohex-5-ene (−)-11
NaN3 (273 mg, 4.20 mmol) and NH4Cl (225 mg, 4.20 mmol) were added to a solution of (−)-10 (290
mg, 1.37 mmol) in DMF (12 ml). After washing with H2O, the organic layer was dried over Na2SO4 and
evaporated to dryness to give a residue that was hydrolysed with MeOH:NH4OH (9:1). Recrystallisation
from EtOAc gave the desired azide (−)-11 (225 mg, 78% yield): mp (dec.) 135–136°C; [α]D −184.9 (c
0.8, EtOH); 1H NMR (D2O) δ 3.37 (1H, dd, J=11.0 and 8.0), 3.45 (1H, dd, J=11.0 and 7.5), 4.08 (2H,
m), 5.54 (2H, m); 13C NMR (D2O) δ 69.7, 70.7, 71.9, 75.2, 129.3, 129.5.

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4.13. 5-Azido-5-deoxy-myo-inositole-pentaacetate meso-12 and 1L-4-azido-4-deoxy-myo-inositole-
pentaacetate (+)-13
N-Methylmorpholine-N-oxide (140 mg, 1.19 mmol) and OsO4 (15 mg, 0.06 mmol) were added to a
solution of (−)-11 (225 mg, 1.07 mmol) in 10 ml of H2O:acetone (1:4) and the mixture was kept at room
temperature for 4 days. The reaction course was monitored by TLC (EtOAc:MeOH=8:2) and when the
substrate had disappeared (96 h) the solvent was evaporated to give a residue which was acetylated under
standard conditions (Ac2O/py). The crude product was chromatographed on Si gel (CHCl3 as the eluent)
to give 12 (149 mg, 34% yield) and (+)-13 (174 mg, 42% yield).
1
12: H NMR (CDCl3) δ 2.03 (6H, s) 2.14 (6H, s), 2.23 (3H, s), 3.64 (1H, t, J=10.3), 5.07 (2H, dd,
J=10.3 and 2.8), 5.41 (2H, t, J=10.3), 5.60 (1H, t, J=2.8); 13C NMR (CDCl3) δ 20.4, 20.6, 20.7, 62.7,
68.1, 68.9, 69.4, 169.4, 169.6, 169.8. Anal. calcd for C16H21N3O10: C, 46.27; H, 5.10; N, 10.12. Found:
C, 46.35; H, 5.08; N, 10.16.
(+)-13: [α]D +14.3 (c 0.4, CHCl3); 1H NMR (CDCl3) δ 2.01 (3H, s) 2.05 (3H, s), 2.11 (3H, s), 2.14
(3H, s), 2.23 (3H, s), 4.01 (1H, t, J=10.5), 4.95 (1H, dd, J=10.5 and 2.8), 5.06 (2H, m), 5.45 (1H, dd,
J=10.5 and 10.4), 5.61 (1H, t, J=2.8); 13C NMR (CDCl3) δ 20.4, 20.5, 20.7, 60.8, 68.2, 68.3, 69.1,
69.6, 71.0, 169.2, 169.3, 169.4, 169.6, 170.0. Anal. calcd for C16H21N3O10: C, 46.27; H, 5.10; N, 10.12.
Found: C, 46.22; H, 5.12; N, 10.18.
4.14. 5-Ammonium-5-deoxy-myo-inositole acetate 14
Compound 12 (140 mg, 0.34 mmol) was dissolved in 5 ml EtOH and hydrogenated in the presence
of Pd/C (10 mg) at barometric pressure and room temperature. After 24 h, the catalyst was filtered off
and the filtrate evaporated to dryness to leave a residue that was hydrolysed with MeOH:NH4OH (9:1)
to give 14 (75 mg, yield 98%); 1H NMR (D2O): δ 2.08 (3H, s), 3.66 (5H, m), 4.11 (1H, m); 13C NMR
(CD3OD) δ 23.4, 56.9, 71.9, 73.1, 176.0.
4.15. 1L-4-Ammonium-4-deoxy-myo-inositole acetate (−)-15
(−)-15 was prepared from (+)-13 by hydrogenation and subsequent hydrolysis following the same
procedure described above for the preparation of 14: [α]D −11.2 (c 0.1, MeOH); 1H NMR (D2O): δ 1.96
(3H, s), 3.61 (4H, m), 4.11 (2H, m); 13C NMR (CD3OD) δ 23.2, 61.5, 69.1, 70.1, 72.3, 76.1, 175.4.
Acknowledgements
The authors are grateful to Novo Nordisk for the gift of Lipozyme® IM and Novozym® 435. This work
has been supported by a grant from CNR under the Scheme ‘Biotecnologie’.
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