1. Asymmetric synthesis of (2S,3S)-3-Me-glutamine and (R)-allo-threonine derivatives proper for solid-phase peptide coupling
Yoshinori Tokairin, Vadim A Soloshonok, Hiroki Moriwaki, Hiroyuki Konno Amino Acids. 2019 Mar;51(3):419-432. doi: 10.1007/s00726-018-2677-5. Epub 2018 Nov 17.
Practical new routes for preparation of (2S,3S)-3-Me-glutamine and (R)-allo-threonine derivatives, the key structural components of cytotoxic marine peptides callipeltin O and Q, suitable for the Fmoc-SPPS, were developed. (2S,3S)-Fmoc-3-Me-Gln(Xan)-OH was synthesized via Michael addition reactions of Ni (II) complex of chiral Gly-Schiff base; while Fmoc-(R)-allo-Thr-OH was prepared using chiral Ni (II) complex-assisted α-epimerization methodology, starting form (S)-Thr(tBu)-OH.
2. Synthesis of orthogonally protected L-threo-beta-ethoxyasparagine
Jan Spengler, Marta Pelay, Judit Tulla-Puche, Fernando Albericio Amino Acids. 2010 Jun;39(1):161-5. doi: 10.1007/s00726-009-0389-6. Epub 2009 Nov 17.
Orthogonally protected L-threo-beta-ethoxyasparagine (Fmoc-EtOAsn(Trt)-OH, 1) was synthesized from diethyl (2S,3S)-2-azido-3-hydroxysuccinate 2 in eight steps as a building block for solid-phase peptide synthesis. The starting material is easily available in multi-gram scale from D-diethyltartrate. The transformation steps reported here are robust and scalable. Thus, a significant amount of 1 (1.8 g) was obtained in 21% overall yield. The synthesis reported is also expected to be useful for the preparation of other O-substituted L-threo-beta-hydroxyasparagine derivatives.
3. Total Synthesis and Structural Establishment/Revision of Antibiotics A54145
Delin Chen, Hoi Yee Chow, Kathy Hiu Laam Po, Wenjie Ma, Emily Lok Yee Leung, Zhenquan Sun, Ming Liu, Sheng Chen, Xuechen Li Org Lett. 2019 Jul 19;21(14):5639-5644. doi: 10.1021/acs.orglett.9b01972. Epub 2019 Jul 2.
A54145 is a family of antibacterial cyclic lipodepsipeptides structurally resembling daptomycin. Since its discovery in 1990, only the ambiguous structures of the methoxy-aspartic acid (MeO-Asp) and the hydroxy-asparagine (HO-Asn) have been reported. We have developed efficient routes to obtain the fully protected l-MeO-Asp and l-HO-Asn building blocks compatible with Fmoc-SPPS, and a total synthesis of A54145 that enabled us to establish its structure, consisting of l-3S-HO-Asn and l-3R-MeO-Asp, revising the wrongly proposed structure of l-3S-MeO-Asp.
