Reinvestigation of tryptophan-dehydrobutyrine diketopiperazine structure

Carmen Avendaño,Nieves Cabezas,Elena De La Cuesta,J Francisco González,Anthony Waring

doi:10.3998/ark.5550190.0006.905

Carmen Avendaño, Nieves Cabezas + Show 3 more

Open Access

https://doi.org/10.3998/ark.5550190.0006.905

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Abstract

Reinvestigation of the title natural product's structure (1) has shown the easy racemization of the Trp-stereocenter in some derivatives of cyclo-L-Trp-Gly. The here described synthesis of compound 2, a regioisomer of 1 with the N-methyl group on the nitrogen adjacent to the ethylidene side-chain, permits us to conclude that structure 1 was correct.

Highlights

Cytotoxic anticancer drugs elicit cellular stress responses which frequently produce a drugresistant phenotype
The main role of glutathione-S-transferase family (GSTs) is to promote the neutralization of electrophilic toxins by the intracellular tripeptide glutathione (γ-glutamylcysteinylglycine),[3] but these enzymes are catalysts of eicosanoid biosynthesis, a mechanism that may be important in anticancer chemotherapy owing to the involvement of those compounds in the control of cellular division.[4]
MI513-bF5, is one of these natural products whose structure was reported in 1974 without a clear assignment of the configuration of the C-(2)- stereocenter and the stereochemistry of the exocyclic double bond.8c,9a Owing to our interest in inhibitors of resistances to antitumor agents,[10] and the experience in aldol reactions with diketopiperazines,[11] we investigated the synthesis of 1 by condensation of acetaldehyde with N-acetyl derivatives of N1-methyl-cyclo-L-Trp-Gly by using a variety of reaction conditions

Summary

Introduction

Cytotoxic anticancer drugs elicit cellular stress responses which frequently produce a drugresistant phenotype. MI513-bF5, is one of these natural products whose structure was reported in 1974 without a clear assignment of the configuration of the C-(2)- stereocenter and the stereochemistry of the exocyclic double bond.8c,9a Owing to our interest in inhibitors of resistances to antitumor agents,[10] and the experience in aldol reactions with diketopiperazines,[11] we investigated the synthesis of 1 by condensation of acetaldehyde with N-acetyl derivatives of N1-methyl-cyclo-L-Trp-Gly by using a variety of reaction conditions.

Results

Conclusion