Total Synthesis of Siomycin A: Construction of Synthetic Segments

Abstract

The five practical segments for the total synthesis of siomycin A, that is, the dehydropiperidine segment A (5), the pentapeptide segment B (3), the dihydroquinoline segment C (6), and the beta-phenylselenoalanine dipeptide segments D (7) and E (4), were synthesized. Segment A (5) was constructed by the coupling of the azomethine ylide and the chiral sulfinimine, followed by the stereoselective reduction of the six-membered imine function. Segment B (3) was synthesized by the phenylselenylation of the beta-lactone, stereoselective vinylzinc addition to the chiral sulfinimine, and oxazoline-thioamide conversion. Segment C (6) was prepared by the one-pot olefination of the tetrahydroquinoline N-oxide using triflic anhydride and triethylamine, stereoselective reduction of the methyl ketone function, and regioselective Yb(OTf)(3)-catalyzed epoxide opening by the amino group. Segments D (7) and E (4) were synthesized by coupling of the properly protected beta-phenylselenoalanines.

Thiopeptide Antibiotics: Retrospective and Recent Advances

“…Their approach was based on formation of a substituted central 1-pyrroline 39 that underwent ring-expansion to form a piperidine ring 37 ( a series) that could be selectively oxidized for form the corresponding 2,3,4,5-tetrahydropyridine 38 ( b series) [162] (Scheme 12). In further reports they described the synthesis of other fragments [163,164] of b series thiopeptides and finally achieved the total synthesis of siomycin A [165,166]. …”

Biomimetic Synthesis of Azole‐ and Aryl‐Peptide Alkaloids

“…Two total syntheses of thiostrepton and the very similar siomycin have been published, the former by the Nicolaou group [37][38][39][40] and the latter by Nakata et al [41,42]. Figure 9.6 summarizes the key disconnections.…”

Chiral Sulfur Compounds Studied by Raman Optical Activity: tert‐Butanesulfinamide and its Precursor tert‐Butyl tert‐Butanethiosulfinate

“…[1][2][3][4][5] One of the simplest sulfinamide, tert-butanesulfinamide, has been established as a versatile reagent for the asymmetric synthesis of aminecontaining compounds, which are prominent in drugs, agrochemicals, and naturally occurring materials. 3 Specifically, tert-butanesulfinamides have been applied in the synthesis of enantiopure sulfinylimines, 6-10 a-branched amines, 6,7,9,[11][12][13] allylic amines, [14][15][16] propargylic amines, 17,18 a-amino acid and b-amino acid derivatives, 8,19-21 1, 2-amino alcohols, 17,22,23 1, 3-amino alcohols, 24,25 1, 2-diamine, 26,27 1, 3-diamines, 28,29 fluorinated amine derivatives, [30][31][32][33][34] a-organometallic amines, 35,36 aziridine, 23,37 and cyclic sulfinamides. 38,39 In asymmetric catalysis, tert-butanesulfinamides are increasingly being incorporated within chiral ligand and organocatalyst frameworks.…”