title: Total syntheses of (-)-pyrimidoblamic acid and P-3A.
abstract: Total syntheses of (-)-pyrimidoblamic acid and P-3A are disclosed. Central to the convergent approach is a powerful inverse electron demand Diels-Alder reaction between substituted electron-deficient 1,2,3-triazines and a highly functionalized and chiral primary amidine, which forms the pyrimidine cores and introduces all necessary stereochemistry in a single step. Intrinsic in the convergent approach is the potential it provides for the late stage divergent synthesis of modified analogs bearing deep-seated changes in either the pyrimidine cores or the highly functionalized C2 side chain common to both natural products. The examination of the key cycloaddition reaction revealed that the inherent 1,2,3-triazine mode of cycloaddition (C4/N1 vs C5/N2) as well as the amidine regioselectivity were unaffected by introduction of two electron-withdrawing groups (-CO2R) at C4 and C6 of the 1,2,3-triazine even if C5 is unsubstituted (Me or H), highlighting the synthetic potential of the powerful pyrimidine synthesis.
authors.affiliation: Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Duerfeldt
authors.forename: Dale L
authors.initials: DL
authors.lastname: Boger
mesh_terms: D000578:Amidines / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001761:Bleomycin / Q000031:analogs & derivatives*; D061565:Cycloaddition Reaction; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D014227:Triazines / Q000737:chemistry*
chemical_list: D000578:Amidines; D000970:Antineoplastic Agents; D004151:Dipeptides; D011743:Pyrimidines; D014227:Triazines; D001761:Bleomycin