Toward The Total Synthesis Of Polyoxins A Kind Of Natural Nucleoside Peptide Antibiotics

The polyoxins formed an important group of nucleoside peptide antibiotics which is comprised of 14 members and isolated from the fermentation broth of Streptomyces cacaoi vat asoensis.Polyoxins are known as antifungal agents that selectively inhibit membrane bound enzyme chitin synthase from yeast and other fungi,including Candida albican,a fungal pathogen which affects immunocompromised humans. Because of their particular bioactivity these compounds were used in the prevention against insect pests widely and it's possible for these compounds to therapy some human disease.The structure of these compounds is exactly similar.Every member of polyoxin was comprised of twoβ-hydroxy-α-amino acid and there are three kinds ofβ-hydroxy-α-amino acid contained in these compounds.A lot of paper reported the synthesis of several mumbers of polyoxins.In this paper we reviewed the synthesis of the three fragments respectively and investigated the synthesis of the three fragments. Tricycloiminolactone and chiral tert-butanesulfinyl amide was employed as chiral auxiliary in the synthesis.At last we developed a common approach to thymine polyoxin C and it's analogues with different pyrimidine base,synthesized 5-O-carbamoyl-2-epi-polyoxamic acid and 2"-epi-Polyoxin J with stereospecific approach for the first time.In addition,synthetic method of Polyoxin M and it's diatstereoinomers was developed.Caprazol,a core structure ofcaprazamycins which were isolated from a culture broth of the Actinomycete strain Streptomyces sp.MK730-62F2,have shown excellent antimycobacterial activity in vitro against drug-susceptible and multidrug-resistant mycobacterium tuberculosis strains and exhibit no significant toxicity in mice.In view of their important bioactivity,many chemists focused their attention on the total synthesis of these compounds.But few related paper was reported by now because of their complex structure.We selected caprazol as our target molecule to investigate the application of tricycloiminolactone and chiral tert-butanesulfinyl amide in the synthesis of complex natural products and constructed the key intermediate of the synthesis and the successive work is in progress.In the synthesis of these compounds,we investigated the application of tricycloiminolactone in the synthesis of complex natural compounds and indicate our research direction of the synthetic methodology based on tricycloiminolactone.In addition to this,we discussed the stereochemistry in the synthesis of polyhydroxyα-amino acid based on chiral tert-butanesulfinyl amide.