Stereoselective Synthesis of Southern Fragment of Hantupeptin-A

Abstract

The stereoselective synthesis of the southern fragment (C21-C41) of Hantupeptin A is described. The required stereochemistry of β-hydroxy-α-methyl acid unit was accomplished through the Aldol reaction using Evan's chiral auxiliary followed by the installation of the terminal alkyne with Ohira-Bestmann reagent.

From Target-Oriented to Motif-Oriented: A Case Study on Nannocystin Total Synthesis

“…Concurrent to Hu and He's work [7] shown in the previous section, Kalesse et al demonstrated the viability of macrolactamization in nannocystin synthesis by utilizing a different scissile peptide bond (Figure 2, method F) [8]. Distinctive of their approach is a joint usage of asymmetric vinylogous Mukaiyama aldol condensation [13,31,32] and vinylogous Horner-Wadsworth-Emmons (HWE) reaction [33] in order to access the polyketide segment 74, to which three amino acids 63, 76, and 77 [34] (boxed in Scheme 6) are added in a stepwise fashion. The synthesis is concluded with macrolactamization and deprotection.…”

Total Synthesis of Nannocystin Ax

“…24 Isoleucine fragment 8 can be obtained from L-isoleucine using the literature procedure. 19 Amidation between northern fragment 4 and isoleucine fragment 8 (Scheme 4) proved to be challenging because of the presence of the N-methylated amine. 25 For this coupling, several sets of conditions were investigated (e.g., PyBrop, PyClop, Oxyma, EDC•HCl, and DMAP), and it was found that (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholino-carbenium hexafluorophosphate (COMU) 26 gave the best results (82%) for these substrates.…”

“…In those syntheses, a cross-coupling between C8 and C9 − or a metathesis between C7 and C8 was performed. The linear precursor could be generated from northern fragment 4 and the three peptide fragments 6 , 7 , and 8 via sequential amidation or esterification reactions. The key steps for the synthesis of 4 were a vinylogous Horner–Wodsworth–Emmons (HWE) reaction and an asymmetric vinylogous Mukaiyama aldol reaction (VMAR) to install the C11 stereocenter.…”

“…Tyrosine fragment 7 (Scheme ) was synthesized by Alloc protection of known 3,5-dichloro- d -tyrosine ( 18 ) . Isoleucine fragment 8 can be obtained from l -isoleucine using the literature procedure …”