Darrell R. Hutchison

A novel approach for total synthesis of cryptophycins via asymmetric crotylboration protocol

Abstract Acyclic and a highly efficient stereoselective C C bond formation of aldehyde 3 with the crotylboron reagent 4 , derived from (−)-α-pinene, provided a homoallylic alcohol 6 in ≥99% enantio-(ee) and diastereomeric excess (de). The alcohol 6 was linearly converted into the desired Fragment A 10 of cryptophycins in seven steps. This enantiomerically pure Fragment A was conveniently and efficiently coupled with the other three fragments, namely B, C and D, and provided the desired cryptophycin A derivative ( LY404291 ). The terminal double bond in LY404291 was further elaborated to provide a terminal epoxide LY404292 , and cryptophycins 51 and 52 .

A simple and general synthesis of 4-oxo-4,5,6,7-tetrahydroindoles via a novel intramolecular 1,3-dipolar cycloaddition approach

Abstract A general synthesis of 4-keto-4,5,6,7-tetrahydroindoles 6–12 has been achieved in two steps using a new intramolecular 1,3-dipolar cycloaddition approach in moderate yields (45–60%). The potential of this methodology is demonstrated by the synthesis of a mitomycin skeleton ( 15 ) and a topoisomerase-1 inhibitor skeleton ( 17 ).

Diastereoselective conjugate addition approach to picenadol and oxygenated analogues

Horner-Emmons-Wadsworth reaction with 1,3-dimethyl-4-piperidone in water afforded an exocyclic enone, with minimal deconjugation of the double bond. Copper catalyzed conjugate addition with an aryl Grignard reagent then afforded an adduct with high stereocontrol. Wolff-Kischner reduction and deprotection proceeded to provide picenadol (1) in excellent overall yield. Access to oxygenated analogues of picenadol was also accomplished with this approach