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Synthesis 2017; 49(21): 4869-4875
DOI: 10.1055/s-0036-1590799
paper
© Georg Thieme Verlag Stuttgart · New York

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
,
Fernando Coelho  *
a   Laboratory of Synthesis of Natural Products and Drugs, Institute of Chemistry, University of Campinas, PO Box 6154, 13083-970, Campinas, SP, Brazil
› InstitutsangabenE.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
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Publikationsverlauf

Received: 21. Mai 2017

Accepted after revision: 24. Mai 2017

Publikationsdatum:
27. Juli 2017 (online)

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Abstract

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.

Key words

LAB-1 - iminosugars - pyrrolidine - Morita–Baylis–Hillman

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1590799.
  • Supporting Information
 

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