Deoxyharringtonine synthesis

Chinese workers have continued their pharmacological exploration of esters of cephalotaxine (3a) and have reported the transformation of this alkaloid into harringtonine (26a)12 and 0-(2-oxo-5-methylhexanoyl)cephalotaxine (26b).13 The latter compound is an intermediate in the synthesis of the antineoplastic alkaloid deoxyharringtonine (26c). The overall conversion of cephalotaxine into deoxyhar-ringtonine (26c) via (26b) has been patented.14 Of twenty-two esters of (-)-... 

Gin utilised the reduction of an alkyl phenyl sulfone in a synthesis of the anti-leukaemia natural product (-)-deoxyharringtonine 61 Treatment of complex sulfone 61 with SmI2-HMPA gave 62 in 74% yield (Scheme 4.51). 

Mikolajczak et al (55) reported the first synthesis of deoxyharringtonine (4) in 1974, as shown in Scheme 25. Lithium 3-methylbutyne acetylide (169)... 

Huang (56) and Li (57) also reported the synthesis of deoxyharringtonine (4) starting from saturated keto acid 172. The only difference in their procedure was the use of the Reformatsky reaction, rather than the lithio acetate, to introduce the acetate portion of the final product (Scheme 25). 

Auerbach et al. (58) described the synthesis of the acid side chain of deoxyharringtonine as shown in Scheme 26, in their attempt to prepare deoxyharringtonine. The unsaturated diester 174 was treated with trifluo-... 

A short synthesis of the dimethyl ester (25 R = Me), produced similarly by transesterification of deoxyharringtonine (13f), has been achieved. " Commercially... 

The problem of deoxyharringtonine (13f) synthesis from cephalotaxine (13d) has been solved in an interesting way (Scheme 2). Treatment of ethyl t-butyl... 

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