Straightforward Synthesis of Chiral Silylated Amino Acids through Hydrosilylation

Abstract

A method using hydrosilylation of unsaturated amino acids was developed and optimised to obtain silylated amino acids. The platinum (Bu4N)2PtCl6 complex was identified as the best catalyst, and the procedure tolerated different unsaturated substrates, silane reagents and protecting groups. Seven silicon‐containing α‐amino acids were prepared in an enantiomerically pure form under mild conditions in good yields with orthogonal protections for versatile use in peptide synthesis.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

A Convergent Synthesis of Carbocyclic Sinefungin and its C‐5 Epimer

“…[12] Protection of the amine group as Cbz-derivative followed by oxidation of the sulfide in the presence of NaIO 4 provided sulfoxide 10 . [13] Boc-protected sulfoxide 11 was prepared by following similar course of reactions. For the subsequent elimination in mesitylene at 170 °C, the Boc-protected derivative 11 provided a complex mixture of unidentified products along with a trace amount of olefin 5 .…”

“…L ‐Methionine ( 7 ) was converted into methyl ester 9 by using thionyl chloride in methanol according to a reported procedure 12. The protection of the amine group as benzyloxycarbonyl (Cbz) derivative followed by oxidation of the sulfide in the presence of NaIO 4 provided sulfoxide 10 13. The tert ‐butoxycarbonyl‐protected (Boc‐protected) sulfoxide 11 was prepared by following similar course of reactions.…”

Resolution of protected silaproline for a gram scale preparation

“…1). Introduction of silylated amino acids in peptides increases lipophilicity (Cavelier et al 2002Mortensen et al 2009;Bains and Tacke 2003;Marchand et al 2008). The octanol-water partition coefficient of FmocSip-OH has been experimentally determined to be 14 times greater than that of Fmoc-Pro-OH (Cavelier et al 2002).…”

α,α′‐Disubstituted Amino Acids with Silylated Side Chains as Lipophilic Building Blocks for the Synthesis of Peptaibol Analogues

“…Since chirality is crucial with respect to biological activity, we investigated a new strategy to obtain such non-coded amino acids in enantiomerically pure form. Recently, we developed a new access to silylated amino acids through hydrosilylation of unsaturated starting material [22]. Conditions were optimized, and the complex [Pt(Bu 4 N) 2 Cl 6 ] was found to be the best catalyst.…”

“…The desired product 20 was isolated in 63% total yield. This new unsaturated substrate was then subjected to a hydrosilylation reaction [24], previously optimized in our group [22]. A preliminary screening of catalysts in different solvents allowed us to discard Pd complexes, Pt 0 complexes, and cis-[Pt(PPh 3 )Cl 2 ].…”