Cephalotaxus alkaloids synthesis

A photochemical preparation of a Cephalotaxus alkaloid synthon (20) has been reported (Scheme 2).10 The readily accessible maleimide (17) was iodinated with iodine and silver trifluoroacetate, in 71% yield, and the resulting compound was transformed in two steps (70% overall yield) into the methylene-pyrrolone (18) by the action of methylmagnesium iodide followed by dehydration. Irradiation of (18) afforded (19) (46% yield), which, by successive hydrogenation and reduction with lithium aluminium hydride, gave the dihydro-pyrrolo[2,l-b][3]benzazepine (20). This derivative has served as a key intermediate in the total synthesis of cephalo-taxine described previously (see Vol. 7 of these Reports). 

Inhibition of protein synthesis in eukaryotic cells by the Cephalotaxus alkaloids harringtonine, homoharringtonine, and isoharringtonine has been studied.16 In model systems, these alkaloids were found not to inhibit any of the initiation steps but to block certain parts of the elongation phase of translation. 

Alder reaction [524, 525]. Danishefsky et al. have used nitroso dienophiles for the synthesis of mitomycin K and antibiotics of the FR 900482 family, the latter ones are structurally unique aziridino-l,2-oxazine derivatives [526-529]. An approach directed to the cephalotaxus alkaloids has been worked out by Fuchs et al. [530], and several indolizidine alkaloids have been prepared by Keck s [531] and Kibayashi s groups [532,533]. Kibayashi et al. also synthesised Nuphar piperidine alkaloids in enantiomerically pure form by means of an asymmetric nitroso Diels-Alder reaction [534]. 

A comprehensive review concerning the synthesis of the Cephalotaxus alkaloids has appeared/ Another review incorporates this subject in the context of the synthesis of alkaloids which embody in part a benzazepine framework/... 

In 1988 and 1990, Fuchs reported a new approach to the synthesis of the Cephalotaxus alkaloids ( )-cephalotaxine (1) (30,31), ( )-ll-hydroxyceph-alotaxine (26) (31), and ( )-drupacine (28) (31), which was based on the exploitation of vinyl sulfones as convenient multifunctional synthons (Schemes 7 and 8). The synthesis of cephalotaxine (Scheme 7) began with the ortho ester 77, obtained from piperonyl alcohol in five steps, which was... 

The Cephalotaxus alkaloids, which were last reviewed in this series in 1984, are discussed by Miah, Hudlicky, and Reed. This chapter is a very thorough review of all of the approaches that have been described for synthesis of these alkaloids, the efforts to explore structure-activity relationships, and the biological and clinical aspects of the Cephalotaxus alkaloids. 

In studies directed toward the synthesis of members of the Cephalotaxus alkaloid family, irradiation of allylsilane iminium ion (129) provided a 70% yield (at 45% conversion) of spiroazacycle (130). ° It should again be noted that this S-cndo-trig cyclization does not occur without photochemical activation (c/. Scheme 25). 

A review on Erythrina and related alkaloids covering the literature from Noventer 1966 to the end of May 1979 has appeared it sutnnarizes the work published on isolation, structure determination, biosynthesis, synthesis and pharmacolc of Erythrina, Hcmoerythrina, and Cephalotaxus alkaloids, and the... 

This report embodies the work published on the isolation, structure determination, and synthesis of Erythrina, Cocculus, Cephalotaxus, and other related alkaloids. 

A reductive radical process has also been developed from aryl halides. Scheme 25.35 shows a cascade reductive process (78 79) used in the synthesis of cephalezomine This alkaloid was isolated from the leaves of Cephalotaxus harringtonia var. nana and shows cytotoxic activity against human epidermoid carcinoma KB cells. 

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