James Quick

Protein kinase C modulators. Indolactams. 1. Efficient and flexible routes for the preparation of (-)-indolactam V for use in the synthesis of analogs

Abstract Three syntheses of the protein kinase C activator, (-)-indolactam V, are described and are compared for their potential utility in the preparation of ILV analogs. In one route the 4-amino functionality is introduced regiospecifically during the construction of the indole portion and enantiomeric control is achieved by the alkylation of the amine with a triflate derived from d -valine. One of the routes affords racemic ILV from which (-)-ILV is obtained by the first reported resolution of an indolactam.

Protein kinase C modulators. Indolactams. 2.1 Alkylation of 4-nitroindole by Grignard reagents. Synthesis of (-)-7-octylindolactam V

Abstract A method for the C-alkylation of 4-nitroindole at the 5 and 7 positions by alkyl Grignard reagents has been developed. The 4-nitro-7-octylindole thus prepared has been used as a starting material for the synthesis of the lyngbyatoxin analog, (-)-7-octylindolactam V.

A regiocontrolled synthesis of codonocarpine

Abstract The total synthesis of the Lunaria alkaloid codonocarpine is described. Regiospecific formation of the macrocycle is achieved by the use of a properly protected spermidine unit.

Macrolide closure via fluorodesilylation a total synthesis of d, 1-17-o-methyllythridine

Abstract A synthesis of the macrolide 17-O-methyllythridine is reported in which cyclization is initiated by fluorodesilylation of a trimethlsilylacetate.

Synthetic studies on the lythraceae alkaloids-IX: Vanadium (V) oxidation of some seco-alkaloids

Abstract Seco-alkaloids 4-7 were treated with VOF 3 and VOCl 3 , under a variety of conditions. No coupled products were detected. However, ring chlorinated and side-chain oxidized products were obtained from the VOCl 3 oxidation of 4 and 7 respectively. The generality of the ring chlorination reaction was confirmed by chlorination of simple 0-methoxy phenols under these conditions to yield 17 and 23 . In certain cases, 21 and 22 , intermolecular coupling occurs in preference to chlorination.

Preparation of Benzyl γ-Benxoyloxybutyrates

Abstract As part of our investigation of intramolecular phenolic coupling reactions we required a series of diesters of the general structure, 5 1. Since esters of γ-hydroxybutyric acid have been prepared by acid2 or base3 catalyzed alcoholysis of γ-butyrolactone, it appeared that the desired esters might be prepared by alcoholysis of the lactone with a benzyloxide followed by trapping the new alkoxide, 1, with an acyl chloride. However, treatment of γ-butyrolactone with sodium benzyloxide under conditions analogous to those used in the preparation of ethyl γ-hydroxybutyrate3 failed to yield any of the corresponding benzyl ester. We were also unable to trap alkoxide 1 by acylation with acetyl chloride or benzoyl chloride.

Treatment of cinnamic acids with polyphosphoric acid

Polyphosphoric acid has been found to isomerize cis-p-methoxycinnamic acid to trans-p-methoxycinnamic acid and to cleave a benzyl ether; however, there is no evidence for the previously reported trans- to cis-isomerization of cinnamic acids.