Depsipeptide fragments

In summary, among the carbodiimide-based methods only the carbodiimide/dialkyl-aminopyridine technique has been widely used in the synthesis of depsipeptides. It usually affords the desired products in moderate or high yield and has good potential for routine use in the esterification of urethane-protected amino acids or peptide fragments even in the case... 

Precursor ions of main fragment ions observed in the El mass spectrum of depsipeptide (HV scan method) [213]... 

Total Synthesis of Depsipeptide HDAC Inhibitors - Routes to the fi-Hydroxy Acid Fragment... 

Disconnection of the depsipeptides at the amide and ester bonds plus the intramolecular disulfide bridge leads to a peptide fragment and a /1-hydroxy acid. Neither of these is particularly daunting by the standards of modern day complex molecule total synthesis. Nevertheless, the molecule as a whole has an intricate array of functional groups that need to be selectively manipulated. 

All the depsipeptides contain a common /3-hydroxy acid, which can be disconnected by an aldol reaction. However, it is an example of an acetate aldol that suffers from poor facial selectivity of the acetate enolate. Many of the auxiliaries and reagent-based conditions that work for propionate and other a-substituted enolates are unsuitable for acetate aldols. In the event, each depsipeptide total synthesis has featured a different route for the synthesis of this /3-hydroxy acid fragment. 

The adopted strategy was a [2 -h 2 -h 2] fragment condensation. Race-mization (about 13%) of the phenylglycine residue was observed during the formation of the ester bond in the dipeptide fragment Z-Thr(Boc-Phg-0-)-OH before construction of the linear ring-opened depsipeptide. Cyclization between N-methylphenylalanine and the (o-phthalimido a-methylamino butyric acid moieties was achieved in 54% yield with EDCI in conjunction with HOBt under high dilution. 

Recently, Schlessinger and co-workers [108, 109, 110] reported an elegant synthesis of the depsipeptide ester fragment (42) of pristinamycin Ilg (virginia-mycin M2) (34). The reaction sequence resulting in the production of the target molecule required six steps and proceeded in 33% overall yield. 

Aurilide (37) is a 26-membered cyclic depsipeptide (see Chapter 11, Subsection 11.5.6) that includes 3 A-methyl amino acids, isoleucic acid, and an aliphatic acid (Scheme 10.14). To elucidate structure-activity relationships, solid-phase peptide synthesis and solution-phase macrolactamiza-tion were planned. The linear precursor 38 was selected based on Yamada s previously reported approach. " The linear cyclization precursor 38 can be synthesized from solid-supported tetrapeptide 39 in two ways. In method A, isoleucic acid 40, aliphatic acid 41, and A-methylalanine 42 are coupled sequentially. An efficient coupling method for ester formation on polymer support is required. In method B, fragment 43 is prepared in advance to avoid ester formation on polymer... 

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