Mark Mellinger

An efficient method for the synthesis of substituted TosMIC precursors

Abstract Substituted tosylmethyl isocyanides (TosMICs) are useful reagents for which no general method of preparation is available. We describe here a high-yielding method for the synthesis of substituted tosylmethyl formamides, which are readily converted to the corresponding isocyanides.

Novel syntheses of camptothecin alkaloids, part I. Intramolecular [4+2] cycloadditions of N-arylimidates and 4H-3,1-benzoxazin-4-ones as 2-aza-1,3-dienes

Abstract The first reported intramolecular [4+2] cycloadditions of both N-arylimidates and 4 H -3,1-benzoxazin-4-ones acting as 2-aza-1,3-dienes are described. Reaction with unactivated alkynes leads to pyrrolo[3,4-b]quinolines which constitute the ABC ring system of camptothecins.

Novel syntheses of camptothecin alkaloids, part 2. concise synthesis of (S)-camptothecins

Abstract A 9-step, convergent total synthesis of ( S )-camptothecin alkaloids is described. The intramolecular [4+2] cycloaddition of an N-arylimidate with an alkyne is used to prepare the alkaloid ABC ring system. 1 The chiral center is derived utilizing Seebachs chemistry 2 for the diastereoselective Michael addition of a chiral dioxolanone enolate to a methylene malonate acceptor. The total synthesis of non-racemic topotecan is accomplished from (S)-10-hydroxycamptothecin in an additional step.

Preparation of mappicine ketones from camptothecins : chemistry of the camptothecin E ring

Abstract Camptothecin and its analogs are thermolyzed at 150–200 °C to yield mappicine ketone derivatives by loss of carbon dioxide from the α-hydroxylactone.