1. (L)-(Trimethylsilyl)alanine synthesis exploiting hydroxypinanone-induced diastereoselective alkylation
A René, N Vanthuyne, J Martinez, F Cavelier Amino Acids. 2013 Aug;45(2):301-7. doi: 10.1007/s00726-013-1492-2. Epub 2013 Apr 26.
A new and efficient synthesis of (L)-(trimethylsilyl)alanine (TMSAla) with suitable protection for use in Solid Phase Peptide Synthesis (SPPS) has been accomplished starting from glycine tert-butyl ester and using hydroxypinanone as chiral inductor. The silylated side chain was introduced by alkylation of the Schiff base intermediate with iodomethyl(trimethylsilane) at -78 °C. Among the different synthetic routes that were tested including several chiral inductors and different Schiff bases, this strategy was selected and afforded (L)-TMSAla in good chemical overall yield with 98 % ee.
2. Bioactive gold(i) complexes with 4-mercaptoproline derivatives
Alejandro Gutiérrez, Carlos Cativiela, Antonio Laguna, M Concepción Gimeno Dalton Trans. 2016 Sep 14;45(34):13483-90. doi: 10.1039/c6dt02000c. Epub 2016 Aug 8.
Unprecedented gold(i) bioconjugates bearing non-proteinogenic amino acid 4-mercaptoproline species as bioorganic ligands have been prepared. Firstly, the synthesis of Boc-Pro(SH)-OMe (1) has been accomplished by standard procedures. The subsequent reaction of 1 with [AuCl(PR3)] gives complexes Boc-Pro(SAuPR3)-OMe (PR3 = PPh3 (2), PPh2Py (3)). Starting from complex 2 several structural modifications have been performed, in addition to the incorporation of a different phosphine in 3, such as the formation of the acid Boc-Pro(SAuPPh3)-OH (4), the synthesis of a dipeptide derivative by coupling the amino acid glycine tert-butyl ester Boc-Pro(SAuPPh3)-Gly-O(t)Bu (5), or the coordination of another gold phosphine fragment to the sulfur atom as in [Boc-Pro(SAuPPh3)2-OMe]OTf (6). The cytotoxic activity in vitro of these complexes has been evaluated against three different tumor human cell lines, A549 (lung carcinoma), Jurkat (T-cell leukaemia) and MiaPaca2 (pancreatic carcinoma). All the complexes displayed excellent cytotoxic activity with IC50 values in the low μM range and even in the nM range in some cases. Structure-Activity Relationships (SAR) observed from this family of complexes opens the possibility of designing more potent and selective promising gold(i) anticancer agents.
3. Chemo-enzymatic synthesis of N-arachidonoyl glycine
L Goujard, M C Figueroa, P Villeneuve Biotechnol Lett. 2004 Aug;26(15):1211-6. doi: 10.1023/B:BILE.0000036597.25673.33.
N-Arachidonoyl glycine was synthesized in a chemo-enzymatic process where glycine tert -butyl ester was acylated by arachidonic acid and the resulted ester was then de-protected to give the final product. Among various lipases tested and chosen for their ability to cleave fatty amides, that from Candida antarctica B gave the best results resulting in a 39% hydrolysis after 24 h. This enzyme was then used for the reverse N-acylation synthesis and gave a 75% product formation after 24 h using methyl ester of arachadonic acid as acyl donor and acetonitrile as solvent. Direct acylation of glycine gave less than 10% yield.
