Stereoselective synthesis of four possible isomers of streptopyrrolidine

Abstract

SummaryThe synthesis of (4R,5R)-streptopyrrolidine (1), (4S,5R)-streptopyrrolidine (2) (4R,5S)-streptopyrrolidine (3) and (4S,5S)-streptopyrrolidine (4) have been achieved in a concise and highly efficient manner via a highly stereoselective aldol type reaction with the trimethylsilyl enolate of ethyl acetate and Lewis acid mediated lactamization as the key reactions in ≈42% yield over six steps starting from D-phenylalanine and L-phenylalanine, respectively. The absolute configuration of the natural product was shown to be (4S,5S) by comparing its spectral and analytical data with the reported values.

Recent advances in deep-sea natural products

“…103 The actinobacterium Pseudonocardia sp. 112 Stereoselective synthesis of the four possible isomers of streptopyrrolidine established the absolute conguration as (4S,5S), 113 and there have been several other synthetic investigations into this novel but structurally unassuming anti-angiogenic compound. The pseudonocardians A-C exhibited cytotoxic activity against three tumour cell lines SF-268 (central nervous system cancer), MCF-7 (breast cancer) and NCI-H460 (lung cancer) with IC 50 values ranging between 0.01 and 0.21 mM.…”

“…(KORDI-3973), obtained from a deep-sea sediment sample collected at the Ayu Trough region in the Philippine Sea, was found to contain the unique benzyl pyrrolidine derivative streptopyrrolidine (62), with signicant anti-angiogenesis activity. 112 Stereoselective synthesis of the four possible isomers of streptopyrrolidine established the absolute conguration as (4S,5S), 113 and there have been several other synthetic investigations into this novel but structurally unassuming anti-angiogenic compound. [114][115][116][117] A further Streptomyces sp.…”