Biosynthesis of the Cephalotaxus Alkaloids

Conifers of the genus Cephalotaxus are members of a monogeneric family of plants (Cephalotaxaceae) that occurs in the Far East. These plants have been found to contain a group of alkaloids of unique structure. The most abundant member of this group is cephalotaxine (1) (Figure 1), which was first isolated1 in 1963. The structure of cephalotaxine was elucidated2 in 1969 by X-ray analysis of the methiodine. In C. harringtonia, cephalotaxine is accompanied by small quantities of related alkaloids3–5, the most important being harringtonine (2), deoxyharringtonine (3), isoharringtonine (4), and homoharringtonine (5) (Figure 1). Each of these four alkaloids possesses significant inhibitory activity against the experimental lymphoid leukemia systems P388 and L-1210 in mice6. In addition to the alkaloids based upon the “cephalotaxane” skeleton, a number of alkaloids containing the “homoerythrina” skeleton occur in C. harringtonia 7. One such compound is 3-epischelhammericine (6) (Figure 1). Schelhammericine itself was originally isolated8 from Schelhammera pedunculata (Liliaceae).