Total Syntheses
of (−)-Pyrimidoblamic Acid
and P‑3A
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Abstract
Total
syntheses of (<b>−</b>)-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 (−CO<sub>2</sub>R) 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