10323. Halichondrins

Description and references

Group of antimitotic, polyether macrolides produced by several marine sponges. Halichondrin B has the most potent bioactivity and is the prototype for the anticancer agent, eribulin, q.v. Isoln from Halichondria okadai Kadota: D. Uemura et al., J. Am. Chem. Soc. 107, 4796 (1985) DOI; and antitumor activity: Y. Hirata, D. Uemura, Pure Appl. Chem. 58, 701 (1986) DOI. Isoln from Axinella sp.: G. R. Pettit et al., J. Med. Chem. 34, 3339 (1991) DOI PubMed. Total synthesis of halichondrin B and norhalichondrin B: T. D. Aicher et al., J. Am. Chem. Soc. 114, 3162 (1992) DOI. Effect on bovine brain tubulin: R. F. Luduena et al., Biochem. Pharmacol. 45, 421 (1993) DOI PubMed. Review of potential production methods: D. Sipkema et al., Biotechnol. Bioeng. 90, 201-222 (2005) DOI PubMed.

Chemical structure

Derivative

Halichondrin A.

Nomenclature

CAS number: 102721-98-2
(1″R,2S,2′S,2″R,3aS,3′aS,3″aR,3″bS,5R,5″R,7S,7′S,7aS,7′aS,8″S,11″,S14″S,16″R,18″R,19″aS,20″aS,21″aR,24″aR,25″aS,26″S,26″aR,30″R,31″aS,32″S,33″aR,38″R)-Tetracontahydro-2″,38″-dihydroxy-7,7′,16″,26″-tetramethyl-10″,17″-bis(methylene)-2-[(1S,3R)-1,3,4-trihydroxybutyl]dispiro[5H-furo[3,2-b]pyran-5,5′-[5H]furo[3,2-b]pyran-2′(3′H),23″(6″H)-[1,5:8,11:14,18]triepoxy[30,32]ethano[2,5]methano[2H,5H,28H]furo[2′,3′:5,6]pyrano[4,3-b]furo[2″,3″:5′,6′]pyrano[2′,3′:5,6]pyrano[3,2-i][1,4,8]trioxacyclopentacosin]-28″-one.
C60H86O21; mol wt 1143.31.
C 63.03%, H 7.58%, O 29.39%.

Derivative

Halichondrin B.

Nomenclature

CAS number: 103614-76-2
12,13-Dideoxyhalichondrin A.
C60H86O19; mol wt 1111.31.
C 64.85%, H 7.80%, O 27.35%.

Properties

Crystalline solid, mp 164-166°. [α]D 58.9° (c = 0.94 in methanol).

Derivative

Halichondrin C.

Nomenclature

CAS number: 101383-38-4
13-Deoxyhalichondrin A.
C60H86O20; mol wt 1127.31.
C 63.93%, H 7.69%, O 28.39%.

Properties

Crystalline solid, mp 169-172°. [α]D 41.6° (c = 0.49 in methanol).