Enantiospecific synthesis of some bioactive amino alcohols and related compounds from cyclohexylideneglyceraldehyde

Article abstract of DOI:10.1016/S0957-4166(99)00059-2

Two bioactive amino alcohols or related derivatives, 2-aminohexadecanol I and erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA hydrochloride) IIa, have been synthesized from some enantiomerically pure 3-alkylglycerols. The required C-3 epimeric 3-

Full text of DOI:10.1016/S0957-4166(99)00059-2

Pergamon
Tetrahedron: Asymmetry 10 (1999) 883–890
Enantiospecific synthesis of some bioactive amino alcohols and
related compounds from cyclohexylideneglyceraldehyde
Anubha Sharma and Subrata Chattopadhyay ∗
Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400 085, India
Received 5 January 1999; accepted 17 February 1999
Abstract
Two bioactive amino alcohols or related derivatives, 2-aminohexadecanol I and erythro-9-(2-hydroxy-3-
nonyl)adenine hydrochloride (EHNA hydrochloride) IIa, have been synthesized from some enantiomerically pure
3-alkylglycerols. The required C-3 epimeric 3-alkylglycerols were, in turn, prepared by simple Grignard addition
to cyclohexylideneglyceraldehyde 1 followed by column chromatography. © 1999 Published by Elsevier Science
Ltd. All rights reserved.
1. Introduction
Amino carbinols have assumed contemporary importance in medicinal chemistry due to their various
biological profiles.1 They may be categorized as adrenaline or ephedrine types, depending on the presence
of the amino group at a primary or a secondary carbon atom. The former can be easily prepared by
reduction of the corresponding cyanohydrins which again can be synthesized via various chemical
and enzymatic routes.2 However, synthesis of the latter class is not so straightforward, especially
when the target contains a primary carbinol function. Very recently, we have shown3 that addition
of Grignard reagents to cyclohexylideneglyceraldehyde 1 provides easy access to the C-3 epimers
of alkanetriol derivatives which are useful chirons for the synthesis of various classes of bioactive
compounds. We envisaged that the products, 3-alkylglycerols, are tailor-made for the synthesis of the
ephedrine type of amino carbinols or more complex related compounds. In this paper, we wish to
report the synthesis of two such compounds, 2-aminohexadecanol I and erythro-9-(2-hydroxy-3-nonyl)-
adenine (EHNA) II, from two 3-alkylglycerols. Compound I was very recently shown4 to possess the
minimum basic structural skeleton as a simpler analogue of the immunosuppressant, ISP1 and reported5
to exhibit immunosuppressive activity comparable to that of FTY720. EHNA on the other hand, has
been implicated as an important inhibitor for adenosine deaminase (ADA).6 This synthetic inhibitor,
∗
Corresponding author.
0957-4166/99/$ - see front matter © 1999 Published by Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00059-2

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despite showing moderate biological activity might emerge as the most desirable co-drug for use against
viruses and cancer in view of its low toxicity, reversible ADA binding and the capacity to prevent the
deamination of chemotherapeutic agents containing adenine bases such as 8-azaadenosine.7 In addition,
ADA-inhibition leads8 to increased levels of adenosine which in turn protects injured tissues in cerebral
and myocardial ischemia.
2. Results and discussion
Given the above importance of the compounds I and II, we explored the Grignard addition approach
to 1 for their synthesis (Scheme 1). Compared to the existing syntheses of I5 and II,9 the present method
is far superior in terms of brevity, simplicity and overall efficiency. For compound I, since its (R)-
antipode was most active, we prepared the eutomer, while for EHNA, we prepared its (2R,3S)-isomer
as its hydrochloride IIa, although (2S,3R)-II is most active among its possible diastereomers. However,
in all cases, the flexibility of the synthetic scheme would allow the preparation of any desired isomer
with equal efficiency.
Scheme 1.
The initial task was the preparation of the required alkylglycerol derivatives for which aldehyde 1 was
reacted with suitable Grignard reagents viz. n-tetradecylmagnesium bromide for I and n-hexylmagnesium
bromide for II, respectively (Scheme 1).
The diastereoselectivity of each of the reactions is shown in Table 1. The resultant syn-carbinols 2a
and 3a and anti-carbinols 2b and 3b were were easily isolated in an enantiomerically pure form by
column chromatography. Their syn- and anti-stereochemistry were confirmed by comparing the 1H NMR
resonances of the -CH2O and -CHO groups with those reported in literature.9a,b In both cases, the high
field (500 MHz) 1H NMR spectra of the syn-compounds 2a and 3a showed three multiplets in the ratio
of 1:1:2 protons between δ 3.5–4.20 while the same for the corresponding anti-compounds 2b and 3b
contained four well separated multiplets (1:1:1:1) at δ 3.7–4.0 (1H). The C-3 epimeric carbinols were
then used for the synthesis of I and IIa, respectively, as discussed below.
Table 1
Stereochemical course of Grignard addition to 1

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885
2.1. Synthesis of I
The triol derivative 2b was tosylated and subjected to azidation with inversion to give compound 5.
However, attempted acidic hydrolysis of its acetal function led to some undesired product along with a
minor amount of 6. Consequently, the tosylate of 2b was directly deacetalized with trifluoroacetic acid
(TFA) to give 7 which was converted to the azide 6. Its NaIO4 cleavage furnished the aldehyde 8 which
on LAH reduction finally afforded the amino alcohol (R)-I (Scheme 2).
Scheme 2.
2.2. Synthesis of IIa
For the synthesis (Scheme 3), the syn-carbinol 3a was benzylated to give 9 which on deacetalization
afforded compound 10. Treatment of this compound with p-TsCl and NaH smoothly furnished epoxide
11 which was reduced to yield the diol derivative 12. After protection of the hydroxyl function as a
tetrahydropyranyl ether 13, the benzyl group was removed by catalytic hydrogenation to give compound
14. This was mesylated and reacted with sodium adenylate to afford compound 15, which upon acid
catalyzed deprotection gave the title compound IIa.
Scheme 3.
Thus, a simple synthetic approach for the syntheses of two different types of amino carbinols or
related compounds has been formulated. The enantiomeric homogeneity of the starting chirons 2b and
1
3a used for the syntheses was established by H NMR spectra. Based on this estimation, the synthetic

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A. Sharma, S. Chattopadhyay / Tetrahedron: Asymmetry 10 (1999) 883–890
target compounds should also be enantiomerically pure. This is also corroborated by comparison of their
chiroptical data with those reported in literature.4,9b
3. Experimental
The IR spectra were scanned as thin films with a Perkin–Elmer spectrophotometer model 837. The 1H
NMR were recorded with a Bruker AC-200 (200 MHz) instrument. The optical rotations were measured
with a Jasco DIP 360 polarimeter. The GLC analyses were carried out with a Chemito instrument fitted
with a DB 5 capillary column (15 M×0.25 mm) using He (1 ml/min) as the carrier gas and under temp.
prog. 80–240°C @ 4°C/min. All anhydrous reactions were carried out under an Ar atmosphere using
freshly dried solvents. Unless otherwise mentioned, the organic extracts were dried over anhydrous
Na2SO4.
3.1. General method of preparation of 2a, 2b, 3a and 3b
To a stirred solution of the Grignard reagent [0.03 mol, prepared from the respective bromide (0.03
mol) and Mg turnings (0.864 g, 0.036 mol)] in THF (60 ml) was added 1 (1.7 g, 0.01 mol) in THF (20
ml). After stirring for 12 h at room temperature, the reaction was quenched with an aqueous saturated
solution of NH4Cl. The organic portion was separated, the aqueous part was extracted with ether and
the combined organic extracts were washed with brine and dried. Removal of the solvent in vacuo and
column chromatography (silica gel, 0–15% EtOAc/hexane) of the residue furnished the respective syn-
and anti-products.
2a: Yield 0.95 g (25.8%); [α]D +1.29 (c 0.9, CHCl3); IR: 3440, 1480, 1380 cm−1; 1H NMR: δ 0.9
22
(dist. t, 3H), 1.32 (br. s, 26H), 1.68 (br. s, 10H), 2.7 (br. s, D2O exchangeable, 1H), 3.48–3.59 (m, 1H),
3.75–3.87 (m, 1H), 4.04–4.24 (m, 2H). Anal. calcd for C23H44O3: C 74.94, H 12.03; found: C 75.12; H
11.88. 2b: Yield 1.37 g (37.2%); [α]D +5.2 (c 0.84, CHCl3); IR: 3380, 1470, 1380 cm−1; 1H NMR: δ
22
0.9 (dist. t, 3H), 1.3 (br. s, 26H), 1.68 (br. s, 10H), 1.9 (br. s, D2O exchangeable, 1H), 3.71–3.78 (m, 1H),
3.82–3.86 (m, 1H), 3.90–3.94 (m, 1H), 3.97–4.02 (m, 1H). Anal. calcd for C23H44O3: C 74.94; H 12.03;
found: C 74.68; H 11.78.
22
3a: Yield 0.76 g (29.7%); [α]D +5.31 (c 0.5, CHCl3); IR: 3440, 1480, 1380 cm−1; 1H NMR: δ 0.88
(dist. t, 3H), 1.3–1.6 (m, 10H), 1.68 (br. s, 10H), 1.8 (br. s, D2O exchangeable, 1H), 3.51–3.60 (m, 1H),
3.82–3.90 (m, 1H), 4.0–4.2 (m, 2H). Anal. calcd for C15H28O3: C 70.27; H 11.01; found: C 70.43; H
11.20. 3b: Yield 1.32 g (51.6%); [α]D +8.53 (c 1.5, CHCl3); IR: 3380, 1470, 1380 cm−1; 1H NMR: δ
22
0.88 (dist. t, 3H), 1.3–1.6 (m, 10H), 1.68 (br. s, 10H), 2.7 (br. s, D2O exchangeable, 1H), 3.77–3.83 (m,
1H), 3.86–3.89 (m, 1H), 3.93–3.96 (m, 1H), 3.98–4.04 (m, 1H). Anal. calcd for C15H28O3: C, 70.27; H,
11.01; found: C 70.39; H 10.86.
3.2. (2R,3R)-3-Azido-1,2-cyclohexylideneheptadecane 5
To a cooled (0°C) and stirred solution of 2b (1.37 g, 3.7 mmol) and pyridine (0.33 ml, 4.09 mmol) in
CH2Cl2 (20 ml) was added p-TsCl (0.852 g, 4.47 mmol). After stirring for 2 h at the same temperature,
the mixture was kept in the freezer for 12 h. It was poured into ice-water, the organic layer was separated
and the aqueous part extracted with CHCl3. The combined organic extract was washed with water and
brine and then dried. Removal of solvent in vacuo followed by column chromatography (silica gel, 0–5%
EtOAc/hexane) of the residue furnished the corresponding tosylate. Yield: 1.77 g (91%); IR: 3090, 3060,

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887
1620, 1460, 1370, 1180 cm−1; 1H NMR: δ 0.86 (dist. t, 3H), 1.32 (br. s, 26H), 1.64 (br. s, 10H), 2.43 (s,
3H), 3.77–3.79 (m, 1H), 3.88–3.93 (m, 1H), 3.96–4.0 (m, 1H), 4.24–4.30 (m, 1H), 7.30 (d, J=8 Hz, 2H),
7.81 (d, J=8 Hz, 2H).
A mixture of the above compound (1.77 g, 3.39 mmol) and NaN3 (0.663 g, 10.2 mmol) in DMF
(20 ml) was gently heated at 80°C for 6 h. After cooling to room temperature, the mixture was poured
into a large excess of cold water and extracted with ether. The ether layer was thoroughly washed with
water and brine. After drying, the extract was concentrated and the crude product purified by column
chromatography (silica gel, 0–5% EtOAc/hexane) to furnish pure 5. Yield: 1.15 g (86%); IR: 2100,
1450, 1280 cm−1; 1H NMR: δ 0.88 (dist. t, 3H), 1.28 (br. s, 26H), 1.64 (br. s, 10H), 3.5–3.54 (m, 1H),
3.81–3.86 (m, 1H), 3.88–4.11 (m, 2H).
3.3. (2R,3S)-3-Tosyloxyheptadecane-1,2-diol 7
A mixture of the tosylate of 2b (1.5 g, 2.87 mmol) in TFA (10 ml) and H2O (5 ml) was stirred for 48
h at 50°C. Most of the solvent was removed under reduced pressure, the residue was diluted with EtOAc
and the organic layer washed with water and brine then dried and concentrated. The product was purified
by column chromatography (silica gel, 0–5% CHCl3/MeOH) to furnish pure 7. Yield: 0.888 g (70%); IR:
3440, 3060, 1640, 1460, 1370, 1180 cm−1; 1H NMR: δ 0.90 (dist. t, 3H), 1.29 (br. s, 26H), 2.37 (s, 3H),
2.6 (br. s, D2O exchangeable, 2H), 3.77–3.93 (m, 3H), 4.17–4.28 (m, 1H), 7.32 (d, J=8.4 Hz, 2H), 7.78
(d, J=8.4 Hz, 2H).
3.4. (2R,3R)-3-Azidoheptadecane-1,2-diol 6
As described earlier, reaction of 7 (0.88, 1.99 mmol) and NaN3 (0.388, 5.97 mmol) in DMF (20 ml)
at 80°C gave 6 after work-up and purification by column chromatography (0–5% MeOH/CHCl3). Yield:
0.504 g (81%); [α]D +3.39 (c 1.3, CHCl3); IR: 3380, 2100, 1450, 1280 cm−1; 1H NMR: δ 0.93 (dist.
22
t, 3H), 1.32 (br. s, 26H), 2.15 (br. s, D2O exchangeable, 2H), 3.53–3.57 (m, 1H), 3.78–3.84 (m, 1H),
3.86–4.08 (m, 2H). Anal. calcd for C17H35O2N3: C 65.13; H 11.25; N 13.41; found: C 65.34; H 11.12;
N 13.18.
3.5. (2R)-2-Azidohexadecanal 8
To a cooled (0°C) and stirred solution of 6 (0.5 g, 1.59 mmol) in CH3CN (30 ml) and H2O (20 ml) was
added NaIO4 (0.684 g, 3.19 mmol) in portions. After stirring for 1 h at the same temperature, the mixture
was filtered and the filtrate concentrated in vacuo. The residue was taken in ether and the extract washed
successively with water, aqueous NaHSO3, water, aqueous Na2S2O3, water, and brine. After drying, the
solvent was removed in vacuo to give pure 8 which was used as such for the next step. Yield: 0.355 g
(79%); IR: 2720, 2100, 1720, 1280 cm−1; 1H NMR: δ 0.89 (dist. t, 3H), 1.32 (br. s, 26H), 4.12–4.28 (m,
1H), 9.71 (d, J=1.5 Hz, 1H).
3.6. (2R)-2-Aminohexadecan-1-ol I
To a cooled (0°C) and stirred suspension of LAH (0.15 g, 3.94 mmol) in ether (30 ml) was added
compound 8 (0.545 g, 1.94 mmol). The reaction mixture was gently refluxed for 3 h, quenched
with aqueous saturated Na2SO4, and the mixture filtered to get rid of the solid precipitate which
was thoroughly washed with EtOAc. The organic extract was concentrated in vacuo and the residue

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chromatographed over silica gel (0–20% EtOAc/hexane) to give I. Yield: 0.348 g (70%); [α]D22 −3.9 (c
0.28, MeOH) (lit.4 [α]D22 −3.7 (c 0.4, MeOH)); IR: 3440, 3060, 3030 cm−1; 1H NMR: δ 0.89 (t, J=6 Hz,
3H), 1.3 (br. s, 24H), 1.51–1.72 (m, 3H), 3.05–3.14 (m, 1H), 3.55–3.68 (m, 2H), 4.87 (br. s, 2H). Anal.
calcd for C16H35ON: C 74.64; H 13.70; N 5.44; found: C 74.48; H 13.52; N 5.61.
3.7. (2R,3R)-3-Benzyloxy-1,2-cyclohexylidenenonane 9
To a stirred suspension of NaH (0.737 g, 15.35 mmol, 50% suspension in oil) in THF (20 ml)
compound 4a (1.31 g, 5.12 mmol) in THF (10 ml) was added. After the brisk evolution of H2 was over,
the mixture was refluxed for 0.5 h, brought to room temperature and BnBr (1.05 g, 6.14 mmol) in THF
(10 ml) added to it. The mixture was subsequently refluxed until the completion of the reaction (∼2 h,
cf. TLC). It was brought to room temperature, poured into ice-water, the organic layer separated and the
aqueous portion extracted with ether. The combined organic extract was washed with water and brine and
then dried. Removal of solvent followed by column chromatography (silica gel, 0–10% EtOAc/hexane)
gave pure 9. Yield: 1.49 g (84%); [α]D +18.1 (c 0.46, CHCl3); IR: 3090, 3030, 1610, 1450, 720 cm−1;
22
1H NMR: δ 0.88 (t, J=6 Hz, 3H), 1.21–1.38 (m, 10H), 1.48–1.83 (m, 10H), 3.48–3.56 (m, 1H), 3.78–3.84
(m, 1H), 3.88–3.96 (m, 2H), 4.55 (s, 1H), 4.62 (s, 1H), 7.35 (m, 5H). Anal. calcd for C22H34O3: C 76.26;
H 9.89; found: C 76.23; H 10.10.
3.8. (2R,3R)-3-Benzyloxynonane-1,2-diol 10
Compound 9 (1.77 g, 5.12 mmol) was deacetalized using TFA (10 ml) and H2O (5 ml) in the same
manner as for compound 7. Identical isolation followed by chromatography of the crude product (silica
gel, 0–5% MeOH/CHCl3) gave pure 10. Yield: 1.0 g (74%); [α]D22+6.7 (c 0.8, CHCl3); IR: 3440, 3090,
1620, 1090, 700 cm−1; 1H NMR: δ 0.90 (t, J=6 Hz, 3H), 1.29 (br. s, 10H), 2.44 (br. s, D2O exchangeable,
2H), 3.51–3.59 (m, 2H), 3.65–3.81 (m, 1H), 4.14–4.61 (m, 3H), 7.35 (s, 5H). Anal. calcd for C16H26O3:
C 72.14; H 9.84; found: C 72.34; H 10.12.
3.9. (2R,3R)-3-Benzyloxy-1-epoxynonane 11
To a stirred suspension of NaH (0.294 g, 6.12 mmol, 50% suspension in oil) in THF (20 ml) was added
compound 10 (0.74 g, 2.78 mmol) in THF (10 ml). After the initial reaction subsided, p-TsCl (0.636 g,
3.34 mmol) in THF (10 ml) was added and the mixture stirred for 4 h at room temperature. The mixture
was poured into ice-water, the organic layer separated and the aqueous portion extracted with ether. The
combined organic extract was washed with water and brine and then dried and concentrated in vacuo.
The residue was chromatographed over silica gel (0–5% EtOAc/hexane) to give pure 11. Yield: 0.360 g
(52%); [α]D22 +31.5 (c 0.42, CHCl3); IR: 3090, 1370, 1215, 1190 cm−1; 1H NMR: δ 0.9 (t, J=6 Hz, 3H),
1.2–1.5 (m, 10H), 2.5–2.7 (m, 2H), 2.8–3.0 (m, 1H), 3.5–4.1 (m, 1H), 4.55 (s, 1H), 4.62 (s, 1H), 7.30 (m,
5H). Anal. calcd for C16H24O2: C 77.37; H 9.74; found: C 77.18; H 9.96.
3.10. (2R,3R)-3-Benzyloxynonan-2-ol 12
To a cooled (0°C) and stirred suspension of LAH (0.165 g, 4.4 mmol) in ether (30 ml) was added
compound 11 (0.72 g, 2.9 mmol). After stirring for 1 h, the reaction was quenched with aqueous saturated
Na2SO4, and the mixture filtered to get rid of the solid precipitate. The organic extract was concentrated
in vacuo and the residue chromatographed over silica gel (0–10% EtOAc/hexane) to give 12. Yield: 0.620

A. Sharma, S. Chattopadhyay / Tetrahedron: Asymmetry 10 (1999) 883–890
889
g (85%); [α]D +42.8 (c 0.28, CHCl3); IR: 3430, 3090, 3030, 1460 cm−1; 1H NMR: δ 0.89 (t, J=6 Hz,
3H), 1.14 (d, J=6 Hz, 3H), 1.2–1.4 (m, 10H), 2.1 (br. s, D2O exchangeable, 1H), 3.5–3.7 (m, 1H), 3.9–4.0
(m, 1H), 4.51 (s, 1H), 4.65 (s, 1H), 7.26 (m, 5H). Anal. calcd for C16H26O2: C 76.75; H 10.47; found: C
76.78; H 10.61.
22
3.11. (2R,3R)-3-Benzyloxy-2-tetrahydropyranyloxynonane 13
A mixture of 12 (0.6 g, 2.4 mmol), DHP (0.242 g, 2.88 mmol) and PPTS (0.02 g) in CH2Cl2 (20 ml)
was stirred at room temperature until completion of the reaction (∼8 h). The reaction was quenched with
10% aqueous NaHCO3, the organic layer separated and the aqueous portion extracted with CHCl3. The
organic extract was washed with water and brine and then dried. Removal of solvent followed by column
chromatography of the residue (silica gel, 0–10% EtOAc/hexane) gave pure 13. Yield: 0.689 g (86%);
22
1
[α]D +15.7 (c 0.78, CHCl3); IR: 3090, 3065, 1450, 870, 810 cm−1; H NMR: δ 0.9 (t, J=6 Hz, 3H),
1.16 (d, J=6 Hz, 3H), 1.3–1.5 (m, 10H), 1.6–1.8 (m, 6H), 3.41–3.59 (m, 2H), 3.82–4.03 (m, 2H), 4.55
(br. s, 0.5H), 4.71 (br. s, 0.5H), 4.9 (s, 2H), 7.32 (m, 5H). Anal. calcd for C21H34O3: C 75.40; H 10.25;
found: C 75.24; H 10.37.
3.12. (2R,3R)-3-Hydroxy-2-tetrahydropyranyloxynonane 14
A mixture of 13 (0.68 g, 2.04 mmol) and 10% Pd–C (50 mg) in EtOH (20 ml) was stirred under a
slight positive pressure of H2 gas. After the required uptake of H2, the mixture was diluted with ether
and passed through a pad (2 in.) of silica gel and the eluent was concentrated in vacuo to give pure 14.
Yield: 0.45 g (90%); [α]D +10.2 (c 0.68, CHCl3); IR: 3440, 880, 810 cm−1; 1H NMR: δ 0.87 (t, J=6
22
Hz, 3H), 1.17 (d, J=6 Hz, 3H), 1.2–1.45 (m, 10H), 1.55–1.7 (m, 6H), 2.16 (br. s, D2O exchangeable, 1H),
3.34–3.63 (m, 2H), 3.73–3.98 (m, 2H), 4.5 (br. s, 0.5H), 4.65 (br. s, 0.5H). Anal. calcd for C14H28O3: C
68.81; H 11.55; found: C 68.74; H 11.43.
3.13. (2R,3S)-3-(Adenin-9-yl)-2-nonanol hydrochloride IIa
To a stirred solution of 14 (0.45 g, 1.84 mmol) in dry pyridine (10 ml) was added methanesulphonyl
chloride (0.235 g, 2.05 mmol). After stirring for 48 h at room temperature, the mixture was poured onto
crushed ice and extracted with CHCl3. The organic extract was washed with water and brine and then
dried. Removal of the solvent gave the crude mesylate which was used as such for the next step in view
of its instability. IR: 1350, 880, 810 cm−1.
To a stirred suspension of pentane washed NaH (0.113 g, 2.36 mmol, 50% suspension in oil) in dry
DMF (10 ml) was added adenine (0.316 g, 2.34 mmol). The mixture was stirred at room temperature for
24 h, HMPA (2 ml) added, followed by the above mesylate in DMF (2 ml), and stirring continued for 7
days at 50°C. It was cooled to room temperature, quenched with MeOH and concentrated in vacuo. Water
was added to the residue which was then extracted with EtOAc. The organic extract was washed with half-
saturated brine, brine and then dried. Solvent removal followed by preparative chromatography (silica
22
gel, 10% MeOH/CHCl3) gave 15. Yield: 0.173 g (26%); [α]D −61.5 (c 0.98, MeOH); IR: 1670, 1600,
870, 820 cm−1; 1H NMR: δ 0.89 (t, J=6 Hz, 3H), 1.22–1.54 (m, 7H), 1.62–2.17 (m, 12H), 3.57–3.72 (m,
3H), 4.45–4.65 (m, 2H), 7.96 (br. s, 2H), 8.42 (s, 1H), 8.72 (s, 1H).
A solution of 15 (0.170 g, 0.5 mmol) in MeOH (10 ml) containing one drop of HCl was stirred at room
temperature for 12 h. Removal of the solvent under vacuum at 40°C gave a gummy product which was
recrystallized from EtOH/ether to obtain IIa. Yield: 0.08 g (54%); [α]D −30.8 (c 0.9, EtOH), (lit.9b
22

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A. Sharma, S. Chattopadhyay / Tetrahedron: Asymmetry 10 (1999) 883–890
[α]D17 −31.7 (c 0.5, EtOH)); IR: 3300, 1680, 1600 cm−1; 1H NMR (d6-DMSO): δ 0.81 (t, J=6 Hz, 3H),
1.18–1.31 (m, 6H), 1.36 (d, J=6 Hz, 3H), 2.43–2.56 (m, 4H), 4.51–4.63 (m, 1H), 4.68–4.78 (m, 1H), 8.5
(br. s, 2H), 8.59 (s, 1H), 8.78 (s, 1H).
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