Structures of harringtonine, isoharringtonine, and homoharringtonine

Anticancer agents from medicinal plants

“…drupacea (Sieb and Zucc.) (Cephalotaxaceae), is another plant-derived agent in clinical use (Itokawa et al, 2005;Powell et al, 1970). A racemic mixture of harringtonine and homoharringtonine has been used successfully in China for the treatment of acute myelogenous leukemia and chronic myelogenous leukemia (Cragg and Newman, 2005;Kantarjian et al, 1996).…”

Drug discovery from natural sources

“…23 , 24 These analogs bind to tubulin leading to morphological changes and then disrupt tumor vasculature, and are in phase II trials. 25 , 26 Homoharringtonine ( 8 ), a cephalotaxus alkaloid from the tree, Cephalotaxus harringtonia found in mainland China, 27 is an inhibitor of protein synthesis and is reported to have activity against hematologic malignancies. 28 Ingenol 3-Oangelate ( 9 ), an analog of the polyhydroxy diterpenoid, ingenol, which was originally obtained from Euphorbia peplus (known as " petty spurge " in England or " radium weed " in Australia), is a potential topical chemotherapeutic agent for skin cancer and exhibits its action through activation of protein kinase C. 29 , 30 Phenoxodiol ( 10 ), a synthetic analog of daidzein, a well known isofl avone from soybean ( Glycine max ), is being developed as a therapy for cervical, ovarian, prostate, renal, and vaginal cancers, and induces apoptosis through inhibition of anti-apoptotic proteins including XIAP and FLIP.…”

Enantioselective synthesis of the ester side chain of homoharringtonine

“…[1][2][3] Research on the biological properties of this alkaloid has shown that HHT inhibits protein biosynthesis in the cell via the breakdown of polyribosomes, the release of completed globin chain, and the inhibition of the initiation of protein synthesis without effecting chain elongation. [4][5] In 2012, omacetaxine mepesuccinate (Synribo), a semisynthetic HHT compound (99.7% purity) was used in studies of chronic myeloid leukemia (CML) and approved by the FDA for the treatment of CML.…”

“…12 This aldehyde was then oxidized to form Robin's acid, which could be attached to the cephalotaxine moiety via Robin's first semisynthesis of HHT. 13 More recently, Yang reported the [2,3]-Meisenheimer rearrangement in the construction of chiral tertiary alcohols in the ester side chain. 14 However, there is still a need for a better and more convenient synthesis of the side chain in order to perform an efficient transformation from cephalotaxine to homoharringtonine.…”