A Convenient Synthesis of 1‐Deoxy‐8a‐epi‐Castanospermine Diastereoisomers (6R,7R,8S,8aS)‐6,7,8‐Trihydroxyindolizidine and (6R,7R,8R,8aS)‐6,7,8‐Trihydroxyindolizidine

Abstract

An efficient synthesis of (6R,7R,8S,8aS)‐6,7,8‐trihydroxyindolizidine and (6R,7R,8R,8aS)‐6,7,8‐trihydroxyindolizidine is described from readily available N‐BOC‐L‐proline, (BOC = tert‐butoxycarbonyl) which involves the addition of ethyl lithiopropiolate to the aldehyde derived from N‐BOC‐L‐proline as a key step, then cyclization to construct indolizidine skeletons and asymmetric dihydroxylation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Asymmetric total synthesis of 1-deoxy-7,8-di-epi-castanospermine

“…As expected, the specific optical rotation of 14 matched well the value reported in the literature for its enantiomer, though opposite in sign {14: [a] 20 D -26.0 (c 1.1, MeOH) vs. ent-14: 7 [a] 20 D +23.5 (c 0.90, MeOH); ent-14: 8a [a] 25 D +23 (MeOH)}. An attentive comparison of 1 H and 13 C NMR data for 14 in our hands with those reported for ent-14 7 and rac-14 6 was made. 1 H NMR data are quite similar for 14 and ent-14, with integrals, multiplicity of resonances and coupling constants largely consistent.…”

“…Here, free base 13 was obtained as a glassy solid by simple filtration and solvent evaporation in a 96% yield for the entire treatment. At this point, the chiro-optical and 13 C NMR data for 13 matched those reported by Ding for the enantiomer of 13 {13: [a] 20 D -10.1 (c 1.9, MeOH); ent-13: 7 [a] 20 D +13.1 (c 0.96, MeOH)}, whilst profound disagreement remained with the data reported by Quintard for rac-13. In this latter case, we surmised that published rac-13 was probably a borane complex, since an almost exact match between our data for 13•BH 3 and those reported for rac-13 was attained (see electronic supplementary information for details, Tables S1 and S2 †).…”

Preparation of γ-siloxyallyltributylstannanes and their use in the synthesis of (±)-1-deoxy-6,8a-di-epi-castanospermine

“…22,23 With regards to their unique properties, (+)-castanospermine 8 and (+)-6-epi-castanospermine 9 and their analogues have recently been synthesized by several groups. [24][25][26][27][28] Among these compounds (+)-1-deoxy-6,8a-di-epi-castanospermine was shown to be an inhibitor of a-L-fucosidase. 29 In order to learn more about this type of molecule both in terms of recognition and structure/reactivity relationships in the area of glycosidase inhibitors, it appears of high interest to synthesise natural and unnatural species in this series with perfect control of the stereochemistry.…”

Recent advances in the synthesis of naturally occurring pyrrolidines, pyrrolizidines and indolizidine alkaloids using proline as a unique chiral synthon

“…Zhang et al achieved the synthesis of two isomers of 1-deoxy-8a-epi-castanospermine 331a and 331b by diastereoselective addition of ethyl lithiopropiolate and Sharpless dihydroxylation as key steps (Scheme 63). 102 The diastereoselective addition of ethyl lithiopropiolate to carbonyl derived from Boc-prolinal 12b in the presence of HMPA afforded the two separable diastereomers 332a and 332b (2.6 : 1). The secondary hydroxyl group of 332a was then protected using TBSCl to afford 333.…”