Edward Piers

Total synthesis of (−)-hemiasterlin, a structurally novel tripeptide that exhibits potent cytotoxic activity

Abstract The total synthesis of (−)-hemiasterlin ( 2 ), a structurally novel, naturally occurring tripeptide that exhibits potent cytotoxic and antimitotic activity against human breast cancer MCF7 cells, is described.

Reaction of (trimethylstanyl)copper(I) reagents with α,β-acettylenic esters: Stereocontrolled synthesis of alkyl (E)- and (Z)-3-tribethylstannyl-2-alkenoates

Abstract The reactions of α,β-actylenic esters 1 with the (trimethylstannyl) copper (I) reagents 4–7 provide good to excellent yields of the corresponding β-trimethylstannyl α,β-unsaturated esters 10 and (or) 11. In nearly all cases studied, except for the reactions involving substrate 1i, the stereochemical outcome of the transformations can be controlled by judicious choice of reagent and (or) reaction conditions. Consequently, both alkyl ( E )- and ( Z )-3-trimethylstannyl-2-alkenoates (10 and 11, respectively) can be produced stereoselectively. The reagents of choice for preparing the ( Z E) Isomers 10 appear to be Me 3 SnCu·Me 2 S (4) and [Me 3 SnCuSPh]Li (5), while reagent 5 must be employed for the efficient, stereoselective production of the ( E Z) isomers 11. Reaction of reagent (5) with substrates 1j and 1k under appropriate conditions provides good yields of methyl 2-trimethylstannyl-1-cyclopentenecarboxylate (42). However, treatment of the esters 1 l and lm with 5 under similar conditions gives the “anomalous” products 44 and 45.

Reaction of (trimethylstannyl) copper reagents with α, β-acetylenic esters

Abstract The stereochemical course of the conjugate addition of various (trimethylstannyl)cuprate (or copper) reagents to α, β-acetylenic esters is dependent on the constitution of the reagent and on the structure of the substrate.

Reaction of β-Diketones with Triphenylphosphine Dihalides: A New, Efficient Synthesis of Cyclic β-Chloro-, β-Bromo- and β-Iodo-α,β-Unsaturated Ketones

Abstract Recently, β-chloro-α,β-unsaturated carbonyl compounds have become increasingly useful as intermediates in organic synthesis. For example, reactions involving a number of different cyclic β-chloro-α,β-unsaturated ketones with a variety of reagents (a malonate anion2, the anion of the dithiolane derivative of ethyl glyoxalate3, zinc-silver couple in methanol4, dimethylsulfoxonium methylide5,6) have produced a series of structurally diverse and potentially fruitful synthetic intermediates. The second-mentioned reagent has also been successfully reacted with a β-chloro-α,β-unsaturated ester3.

Synthesis of vinylcyclopropanes via palladium-catalyzed coupling of cyclopropylzinc halides with vinyl iodides. Total syntheses of (±) -prezizanol and (±)-prezizaene

Abstract Palladium(O)-catalyzed coupling of cyclopropylzinc halides, readily prepared from the corresponding cyclopropyl (tri- n -butyl)stannanes, with vinyl iodides provides good yields of functionalized vinylcyclopropanes. The coupling reaction is used as a key step in total syntheses of the sesquiterpenoids (±)-prezizanol and (±)-prezizaene.

Total synthesis of cis-clerodane diterpenoids: (–)-agelasine A and (+)-(3R,4S,5R,8S,9R,10S)-3,4-epoxyclerod-13-en-15,16-olide

The preparation of the enantiomerically homogeneous bicyclic iodide 26 and its use as a key intermediate for the total syntheses of the cis-clerodane diterpenoids (–)-agelasine A 5 and (+)-( 3R,4S,5R,8S,9R,10S)-3,4-epoxyclerod-13-en-15,16-olide 6 are described.

Intermolecular copper(I) chloride-mediated coupling of alkenyltrialkylstannane functions: A convenient synthesis of conjugated diene systems

Abstract A novel copper(I)-mediated coupling of alkenyltrialkylstannane functions is reported. Thus, treatment of the functionalized stannanes 1–11 with 2.5 equivalents of CuCl in N,N-dimethylformamide (DMF) at room temperature provides good-to-excellent yields of the dienes 12–21 .

Total syntheses of the diterpenoids (−)-kolavenol and (−)-agelasine B

Abstract The trans -clerodane diterpenoids (−)-kolavenol ( 2 ) and (−)-agelasine B ( 1 ) have been prepared from the enantiomerically pure decalone 3 . The key steps of the syntheses involve the stereoselective alkylation of the nitrile 4 (to give 5 ), the efficient coupling of the iodides 10 and 11 to produce the clerodane skeleton 12 , and the electrochemical reduction of 16 to provide (−)- 1 .

Preparation and alkylation of cyclic β-trimethylstannyl α,β-unsaturated esters. A new, general annulation sequence

Abstract The key steps of a newly developed annulation method involve (a) reaction of cyclic β-trifluoromethanesulfonyloxy α,β-unsaturated esters (e.g. 14–16) with lithium (phenylthio)(trimethylstannyl)cuprate, (b) alkylation of the resultant products (e.g. 17–19) with 1,ω-dihaloalkanes, and (c) transmetalation-cyclization of suitable substrates (e.g. 25, 26, 28, 30) derived from the alkylation products (e.g. 20–24).

Thermal rearrangement of divinylcyclopropane systems. A new formal total synthesis of (±)-quadrone

Abstract The key step of a new approach to the total synthesis of the structurally and physiologically interesting sesquiterpenoid (±)-quadrone ( 1 ) involves thermal (Cope) rearrangement of the highly functionalized divinylcyclopropane derivative 8 . The product 9 of this process is converted into 19 , thus completing a formal total synthesis of (±)- 1 .