1. Synthesis of the marine sponge cycloheptapeptide phakellistatin 5(1)
G R Pettit, B E Toki, J P Xu, D C Brune J Nat Prod. 2000 Jan;63(1):22-8. doi: 10.1021/np990253+.
Phakellistatin 5 (1), a constituent of The Federated States of Micronesia (Chuuk) marine sponge Phakellia costada, was synthesized by solution-phase and solid-phase techniques. Because the linear peptide bearing (R)-Asn resisted cyclization, the synthesis of this peptide was repeated using the PAL resin attachment proceeding from N-Fmoc-D-Asp-alpha-OCH(2)CH=CH(2). After addition of the final unit (Ala), the allyl ester was removed under neutral conditions with Pd(o) [P(C(6)H(5))(3)](4). Removal of the final Fmoc-protecting group and cyclization with PyAOP provided (R)-Asn-phakellistatin 5 (2) in 28% overall yield. The same synthetic route from (S)-Asp led to natural phakellistatin 5 (1) in 15% overall recovery. The solution-phase and solid-phase synthetic products derived from (S)-Asp were found to be chemically but not biologically identical with natural phakellistatin 5 (1). This important fact suggested that a trace, albeit highly cancer-cell growth inhibitory, constituent accompanied the natural product or that there is a subtle conformational difference between the synthetic and natural cyclic peptides.
2. Chiral N-Fmoc-beta-amino alkyl isonitriles derived from amino acids: first synthesis and application in 1-substituted tetrazole synthesis
Vommina V Sureshbabu, N Narendra, G Nagendra J Org Chem. 2009 Jan 2;74(1):153-7. doi: 10.1021/jo801527d.
A novel class of optically active N-Fmoc-protected amino isonitriles has been described for the first time. Conversion of the carboxyl group of Fmoc-beta-amino acids into an isocyano group has resulted in a new class of N-urethane-protected amino isonitriles. All the isonitriles have been isolated as stable solids, purified, and completely characterized. A synthetic application of the obtained isonitriles has also been demonstrated through the synthesis of 1-substituted tetrazole analogues of amino acids via a 2 + 3 cycloaddition with trimethylsilyl azide.
3. Efficient asymmetric synthesis of (S)- and (R)-N-Fmoc-S-trityl-alpha-methylcysteine using camphorsultam as a chiral auxiliary
Satendra Singh, Samala J Rao, Michael W Pennington J Org Chem. 2004 Jun 25;69(13):4551-4. doi: 10.1021/jo049622j.
(1R)-(+)-2,10- and (1S)-(-)-2,10-camphorsultam were acylated with ethyl 2-phenylthiazoline 4-carboxylate to afford (+)- and (-)-2-phenylthiazolinylcamphorsultam, which were stereoselectively alkylated with MeI in the presence of n-BuLi. Alkylation of these phenylthiazolinylcamphorsultams occurred from the beta-face rather than alpha-face, resulting in the formation of (S)-alpha-methylcysteine from (1R)-(+)-2,10-camphorsultam and (R)-alpha-methylcysteine from (1S)-(-)-2,10-camphorsultam after acidic hydrolysis. Subsequent protection of the side chain thiol group with trityl alcohol and alpha-amine function with Fmoc-OSu furnished fully protected (S)- and (R)-N-Fmoc-S-trityl-alpha-methylcysteine in overall 20% yield.
