A Short, Organocatalytic Formal Synthesis of (−)-Swainsonine and Related Alkaloids

Abstract

A short synthesis of hydroxyalkyl dihydropyrroles has been developed that involves the coupling of propargylamines with α-chloroaldehydes, followed by Lindlar reduction and a one-pot epoxide formation/opening sequence. The application of this process to the synthesis of unnatural iminosugars and a formal synthesis of (-)-swainsonine is described.

Identification of the Polyketide Biosynthetic Machinery for the Indolizidine Alkaloid Cyclizidine

“…5–6 Recently, the first total synthesis of CLD was reported; however, only the enantiomer was obtained in 26 steps with an overall yield of 2.7%. 5 The complexity in the molecular structure of CLD and the difficulty in its organic synthesis thus make the study of its biosynthetic pathway interesting.…”

Metal-mediated synthesis of pyrrolines

“…Due to the remarkable breadth of their reactivity, pyrrolines are useful intermediates in the preparation of more complex heterocycles. [24][25][26][27][28][29][30][31][32][33][34][35][36][37] A variety of well-established methods of pyrrolines synthesis are available. 38,39 These methods include intramolecular cyclizations of bifunctional compounds and multi-component cyclizations, [39][40][41][42][43][44][45] 1,3-dipolar cycloadditions, [46][47][48][49][50][51] photo-and thermoinduced reactions, [52][53][54] and ring expansion of aziridines, 55,56 among others.…”

A Convenient Synthesis of 1,2‐Disubstituted‐cis‐3,4‐Dihydroxypyrrolidines via an Ugi‐Four‐Component‐Reaction/Cycloisomerization/Dihydroxylation Protocol

“…[48,49] The method proved to be general for substrates bearing aromatic (17a-17f and 18a-18f ), heteroaromatic (17g and 18g), and aliphatic (17h-17r and 18h-18r) motifs (Scheme 4). In this paper, we report the development of a selective method for the synthesis of 1,2-disubstituted-cis-3,4-dihydroxypyrrolidines [a] 4588 Scheme 2.…”

“…[48,49] The method proved to be general for substrates bearing aromatic (17a-17f and 18a-18f ), heteroaromatic (17g and 18g), and aliphatic (17h-17r and 18h-18r) motifs (Scheme 4). Treatment with Full Paper a solution of OsO 4 (4 mol-%) and NMO (N-methylmorpholine N-oxide; 1.5 equiv.)…”

“…in acetone/H 2 O (1.5:1.0) turned out to be the best reaction conditions. [48,49] The method proved to be general for substrates bearing aromatic (17a-17f and 18a-18f ), heteroaromatic (17g and 18g), and aliphatic (17h-17r and 18h-18r) motifs (Scheme 4). Remarkably, this route allowed the construction of dipeptide-type molecules such as 3,4-dihydroxypyrrolidine 17l and 18l (71 %), and thus it opens up new possibilities for the design of peptides.Scheme 4.…”