Conversion of L-Cysteine into D-α-Amino Acids and Related Transformations

• Published in: European Journal of Organic Chemistry 2011-08, Vol.2011 (24), p.4667-4680
• Main Authors: Duthaler, Rudolf O., Wyss, Bernhard
• Format: Article
• Language: English
• Subjects: Amino acids; Chemistry; Chiral pool; Cysteine; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Kinetics and mechanisms; Noncondensed benzenic compounds; Organic chemistry; Preparations and properties; Reactivity and mechanisms; Singlet oxygen; Synthetic meth­ods
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201100247

Naturally configured cysteine is converted into 4‐substituted thiazolidines via the 4‐carbaldehyde corresponding to the serine derived Garner's aldehyde. The key transformation is the conversion into 5‐thiazolidinones by 1O2 oxidation, and fragmentation of the primary 5‐hydroperoxides under in situ acetylating conditions. Whereas the reagent couple trimethylsilyl halides/phenol selectively cleaves the N‐Boc group, LiOH/H2O2 transforms the thiol lactones into lactones by an unknown mechanism, and, subsequently, also cleaves the acetonide affording N‐Boc‐protected D‐amino acids without loss of optical activity. This sequence tolerates unsaturated residues with sensitive allylic functions. In some cases, double bond isomerization is, however, observed. Thethiazolidine intermediates can be cleaved with 3‐nitro‐2‐pyridinesulfenyl chloride, giving reactive mixed disulfides. L‐Cysteine is transformed without loss of optical purity into 4‐substituted thiazolidines, which can readily be transformed into 5‐thiazolidinones by 1O2. Treatment with LiOH/H2O2 gives N‐Boc protected D‐amino acids via the corresponding oxazolidinones. The scope is rather broad, and unsaturated residues R1 with delicate allylic functions are tolerated.