An Improved Synthesis of the Antibiotic Dehydrophos. Issue 29 (10th July 2018)

• Record Type: Journal Article
• Authors: Jiménez‐Andreu, M. Mercedes; Sayago, Francisco J.; Cativiela, Carlos
• Is Part Of: European journal of organic chemistry. Issue 29(2018)
• Page Start: 3965
• Page End: 3973
• Publication Date: 2018-07-10
• Subjects: Dehydrophos -- Natural products -- Aminophosphonic acids -- Peptides -- Total synthesis; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201800689
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : Within this work an efficient procedure for the synthesis of the vinyl phosphonate tripeptide dehydrophos is described. This procedure constitutes a significant improvement over previously described strategies, since critical transformations in the synthesis of dehydrophos were carried out in only two synthetic steps, with higher yields and under smooth conditions. Thus, the dehydrophosphoalanine residue was generated by means of the Horner–Wadsworth–Emmons reaction of formaldehyde with a peptide bearing an aminomethylbis(phosphonate) moiety, whereas deprotection of the N ‐terminal position of the thus‐obtained dehydrophosphonopeptide and partial hydrolysis of the dimethyl phosphonate residue took place simultaneously. In addition, we confirmed that the chiral integrity of the leucine residue was preserved throughout these transformations. Abstract : An improved procedure for the synthesis of the antibiotic dehydrophos is described. Key transformations leading to the desired compound were carried out in only two synthetic steps, with higher yield after easy purification by means of a weakly acidic resin.