Asymmetric synthesis of (−)-(R)-pyrrolam A starting from (S)-malic acid

Efficient asymmetric syntheses of alkaloids and medicinally relevant molecules based on heterocyclic chiral building blocks

“…The synthesis started from the known malimide [22] 17, which was converted to the γ-lactam 2-pyridyl sulfone 18 in three steps. The key SmI 2 -mediated cross coupling of sulfone 18 with methyl acrylate underwent smoothly in the presence of t-BuOH at -60 °C to produce the desired product 19 as a single diastereomer in 90 % yield.…”

“…3) is the one that attracts the most attention because of its remarkable bioactivity and challenging structural feature (bearing five contiguous chiral centers). Castanospermine (22), and its congener 7-deoxy-6-epi-castanospermine (23) were isolated [27] from the seeds of Castanospermum australe and the dried pod of Alexa leiopetala. Possessing powerful and selective inhibitory activities towards α-and β-glucosidases [28], castanospermine (22) A very attractive convergent retrosynthetic analysis of castanospermine (22) and analogues is outlined in Scheme 5 [30].…”

“…Castanospermine (22), and its congener 7-deoxy-6-epi-castanospermine (23) were isolated [27] from the seeds of Castanospermum australe and the dried pod of Alexa leiopetala. Possessing powerful and selective inhibitory activities towards α-and β-glucosidases [28], castanospermine (22) A very attractive convergent retrosynthetic analysis of castanospermine (22) and analogues is outlined in Scheme 5 [30]. The synthon B/ C-based methodologies (approach A) is challenging, however, due to β-elimination [31] of carbanions B/ C, quick proton exchange of carbanion C [32], low stereoselectivity in C-C bond formation and difficult access to the enantiomeric pure forms of carbanion B/C [30].…”

“…We have previously developed C-5-alkylation reaction with alkyl halides using chiral building block 3 as a synthetic equivalent of the heterocyclic synthons G and H [33]. For the synthesis of castanospermine (22) and analogues, the vinylogous aldol reaction of 3 was investigated.…”

New Developments in the Synthesis of Anisomycin and Its Analogues

“…Reductive alkylation of (S)-N,O-dibenzyl malimide 117, prepared from (S)-malic acid [86], with pmethoxybenzylmagnesium chloride gave the α-hydroxylactam 118 as a diastereomeric mixture. Hydroxylactam 118 in the presence of 3 equivalents of boron trifluoride etherate was reduced with excess of triethylsilane to yield predominantly trans-119 in 94.8% yield.…”