Chirality extension of an oxazine building block en route to total syntheses of (+)-hyacinthacine A₂ and sphingofungin B

Abstract

Concise and stereocontrolled syntheses of (+)-hyacinthacine A2 and sphingofungin B were achieved via a diastereomerically enriched oxazine intermediate. The key strategies include palladium(0)-catalyzed intramolecular oxazine formation and diastereoselective nucleophilic addition to an aldehyde. (+)-Hyacinthacine A2 was synthesized in 13 steps and 10.2% overall yield and the synthesis of sphingofungin B proceeded in a linear sequence over 15 steps and 6.9% overall yield from (R)-methyl 2-benzamido-3-((tert-butyldimethylsilyl)oxy)propanoate.

Does thermotropic liquid crystalline self-assembly control biological activity in amphiphilic amino acids? – tyrosine ILCs as a case study

“…In particular, amino acid-derived ILCs are promising candidates in that respect, as they resemble naturally occurring antimicrobial amino acid-containing lipids. 26–28 Because of their amphiphilic character and the relation to lipids which are essential building blocks in the lipid bilayer of bacterial cells, ILCs might be able to interact with and disrupt bacterial cell membranes. These properties would be highly desirable as they might contribute to the development of new antibiotics to counteract the increasing incidence of antibiotic resistance.…”

Recent advances in the total synthesis of polyhydroxylated alkaloids via chiral oxazines

“…2c) are characterized by a bicyclic 1-azabicyclo[3.3.0]octane core. Compounds such as (+)-hyacinthacine A 2 ( 12 ), 17 containing four consecutive stereocenters, belong to this group. Additionally, other diastereomerically enriched natural products like (+)-australine ( 13 ), 16 (+)-alexine ( 14 ), 18 (−)-7- epi -alexine ( 15 ), 18 and (+)-casuarine ( 16 ) 19 are known to exist.…”

A Modular Approach to the Antifungal Sphingofungin Family: Concise Total Synthesis of Sphingofungin A and C

“…Due to their intriguing structural features and important pharmacological properties, sphingofungins became quickly popular total synthetic targets. Until today, 14 distinct synthetic strategies have been applied in the total synthesis of sphingofungins B, D, E, and F,[ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ] with the last syntheses of sphingofungin E and F being reported in 2017 by Noda et al. [35] and Sugai et al.…”