Total synthesis of Cephalotaxus alkaloids

Abstract

modifications of known procedures.5-' Reduction of 10 with lithium aluminum hydride gave an alcohol (11, 96 z yield)* which was converted to p-nitrobenzenesulfonate ester 5 uia the sodium alkoxide of 11 (from sodium hydride-tetrahydrofuran) and p-nitrobenzenesulfonyl chloride (2 equiv) in tetrahydrof~ran.~ The yellow crystalline sulfonate ester (5) is obtained in 92 yield, mp 143-144". ences in the fine structure of the nmr and ir spectra. Both bridgehead olefins are probably produced by the Hofmann route, and, by analogy with the t h e r m o l y~i s~~ of 1 -bicyclo[4.2.l]nonyltrimethylammonium hydroxide, it is likely that the A'(') olefin is the major olefin from this reaction. Thus, we conclude that bridgehead olefin 1 is formed in good yield from the thionocarbonate 13 and that both bridgehead olefins 1 and 2 are probably formed in small amounts in thermolysis of quaternary ammonium hydroxide 4. We are continuing to investigate synthetic routes to 1 and 2 in the hope that we can prepare them under mild conditions and record their spectra.

Palladium‐Catalyzed α‐Arylation Reactions in Total Synthesis

“…In the presence of a Pd(PPh 3 ) 2 Cl 2 /dppe [1,2‐bis(diphenylphosphanyl)ethane, 16 ] catalytic system with Cs 2 CO 3 as the base, a chemo‐ and regioselective α‐arylation was achieved, with preference for the desired ketone functionalization over the amide. Earlier attempts directed towards the synthesis of cephalotaxinone were based on the generation of aryne intermediates and subsequent trapping with nucleophiles 29. Yields in those cases were very low (13–16 %) because the harsh conditions employed resulted in deleterious side reactions.…”

Characterization of select members of the Taxane family using Raman spectroscopy

“…1 are important precursors because they are used to semisynthesize taxol and its analogues. 20 Cephalotaxine is a natural pentacyclic alkaloid 21 used to synthesize related alkaloids which have inhibitory activity against certain types of leukemia. 22 (Fig.…”

Collective Asymmetric Total Synthesis of C‐11 Oxygenated Cephalotaxus Alkaloids

“…The key challenges associated with the synthesis of Cephalotaxus alkaloids are the construction of the azaspiranic tetracyclic core and the stereocontrolled functionalization of the sterically encumbered cyclopentene D ring. Since the first total syntheses of cephalotaxine ( 1 ) by Weinreb [9a] and Semmelhack [9b] in 1972, a large number of groups have continued to investigate different approaches toward the total synthesis of this family of alkaloids [9, 10] . A number of elegant total syntheses of cephalotaxine ( 1 ) and its relatives have been accomplished.…”