Short and Diastereoselective Total Synthesis of the Polyhydroxylated Pyrrolidine LAB-1: A Potent α-Glycosidase Inhibitor
Erica C. da Silva
a
Laboratory of Synthesis of Natural Products and Drugs, Institute of Chemistry, University of Campinas, PO Box 6154, 13083-970, Campinas, SP, Brazil
,
Nathália C. G. Yamakawa
a
Laboratory of Synthesis of Natural Products and Drugs, Institute of Chemistry, University of Campinas, PO Box 6154, 13083-970, Campinas, SP, Brazil
,
Alcindo A. Dos Santos
b
Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes, 748, Cidade Universitária, 05508-000, São Paulo, SP, Brazil Email: coelho@iqm.unicamp.br
a
Laboratory of Synthesis of Natural Products and Drugs, Institute of Chemistry, University of Campinas, PO Box 6154, 13083-970, Campinas, SP, Brazil
› Author AffiliationsE.C.S. thanks São Paulo Research Foundation (FAPESP) for a fellowship (process #2013/06757-6). F.C. thanks FAPESP for financial support (process #2013/07600-3 and 2013/10449-5). A. A. Dos Santos thanks FAPESP for financial support (process # 2016/09579-0); F.C. thanks also the National Council for Scientific and Technological Development (CNPq) for a research fellowship
We described herein a total synthesis of 1,4-dideoxy-1,4-imino-l-arabinitol [(2S,3S,4S)-2-(hydroxymethyl)pyrrolidine-3,4-diol, LAB-1], a polyhydroxylated pyrrolidine, which has been demonstrated to be a selective and potent α-glycosidase inhibitor. The main features of our approach are its shortness, efficiency, and simplicity. The total synthesis was accomplished in 6 steps with an overall yield of 12%, starting from a chiral optically active Morita–Baylis–Hillman (MBH) adduct prepared (without epimerization), from Garner’s aldehyde. As far as we know, this is the first report describing the total synthesis of this biologically active pyrrolidine by exploring the synthetic versatility of a MBH adduct.
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Some years ago, we have described an experimental protocol for the MBH reaction with a chiral α-aminoaldehyde, where no racemization was observed. Unfortunately, this result was revealed to be not so robust, see:
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