A convenient conversion of terminal alkenes into homologous unsaturated and doubly unsaturated esters.

Unsaturated and doubly unsaturated esters have been synthesized in two steps by the application of a radical xanthate transfer process of a simple methylsulfoxide starting material to a range of terminal alkenes. syn-Elimination of the sulfoxide gives α,ß-unsaturated esters, which coupled with a xanthate elimination yields α,ß,γ,δ-unsaturated esters.

Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 1: quaternary amines.

We report the identification of a novel series of human epithelial sodium channel (ENaC) blockers that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. Following a rational design hypothesis a series of quaternary amines were prepared and evaluated for their ability to block ion transport via ENaC in human bronchial epithelial cells (HBECs). Compound 11 has an IC(50) of 200nM and is efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED(50) of 44µgkg(-1) at 1h. As such, pyrazinoyl quaternary amines represent the first examples of a promising new class of human ENaC blockers.

Total synthesis of the Amaryllidaceae alkaloid clivonine.

Two syntheses of the Amaryllidaceae alkaloid clivonine (1) are described. Both employ previously reported 7-arylhydrindane 6 as an intermediate but differ in the method employed for subsequent introduction of what becomes the ring-B lactone carbonyl carbon (C7). The synthesis featuring a Bischler-Napieralski reaction for this transformation constitutes the first asymmetric synthesis of natural (+)-clivonine. Crystal structures for compounds (±)-13, (±)-16, (-)-20 and (±)-28 are also reported.

(±)-trans,cis-4-Hydroxy-5,6-di-O-isopropylidenecyclohex-2-ene-1-one: synthesis and facile dimerization to decahydrodibenzofurans.

An efficient synthesis of (±)-trans,cis-4-hydroxy-5,6-di-O-isopropylidenecyclohex-2-ene-1-one (3) has been developed from acetonide-protected meso-1,2-dihydrocatechol derivative 1 via photooxygenation, then Kornblum-DeLaMare rearrangement. The product is unstable unless its 4-hydroxy group is protected, as it undergoes facile dimerization in solution to a 1:1 mixture of diastereoisomeric decahydrodibenzofurans 8 and 9. A new synthesis of the dihydrocatechol 1 from 1,3-cyclohexadiene has also been developed.

Total synthesis of the lycorenine-type amaryllidaceae alkaloid (+/-)-clivonine via a biomimetic ring-switch from a lycorine-type progenitor.

A fully diastereoselective total synthesis of the lycorenine-type Amaryllidaceae alkaloid (+/-)-clivonine (19) is reported via a route that employs for the first time a biomimetic ring-switch from a lycorine-type progenitor, thereby corroborating experimentally the biogenetic hypothesis first expounded for these compounds by Barton in 1960.