Total Synthesis of (±)-Flustramines A and C, (±)-Flustramide A, and (−)- and (+)-Debromoflustramines A

• Published in: Journal of organic chemistry 2008-08, Vol.73 (15), p.5959-5964
• Main Authors: Kawasaki, Tomomi, Shinada, Masashi, Ohzono, Mayu, Ogawa, Atsuyo, Terashima, Romi, Sakamoto, Masanori
• Format: Article
• Language: English
• Subjects: Bromine Compounds - chemical synthesis; Bromine Compounds - chemistry; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Indole Alkaloids - chemical synthesis; Indole Alkaloids - chemistry; Molecular Structure; Organic chemistry; Preparations and properties
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo800984a

Here we describe the efficient total synthesis of the three title hexahydropyrrolo[2,3-b]indole alkaloids and debromo derivative from readily available indolin-3-ones using key domino reactions, olefination−isomerization−Claisen rearrangement (OIC), and reductive cyclization (RC). (±)-Flustramine C (5) was synthesized in five steps from 6-bromoindolin-3-one 9 via a key intermediate 13a. (±)-Flustramine A (1) has been obtained by reduction of flustramide A (6), which has been prepared in five steps from 13a. (±)-Debromoflustramine A (19) was provided in a similar manner from 13b. The (−)- and (+)-enantiomers of 19 were synthesized through optical resolution of (±)-carboxylic acid 17b using (R)-4-phenyloxazolidin-2-one.