Epothilones
Title: Epothilones
Literature References: Microtubule stablilizing 16-membered macrolides which mimic the biological effects of paclitaxel, q.v., while retaining multidrug-resistant activity. Structurally lacking the taxane ring. Isoln of A and B from the myxobacterium Sorangium cellulosum: G. Höfle et al., DE 4138042, (1993 to Ges. Biotech. Forsch.), C.A. 120, 52841 (1994). Purification of A and B, and mechanism of action: D. M. Bollag et al., Cancer Res. 55, 2325 (1995). Total synthesis of A: A. Balog et al., Angew. Chem. Int. Ed. 35, 2801 (1996); of B and D: D.-S. Su et al., ibid. 36, 757 (1997). Crystal structure of A and B, and conformation in soln: G. Höfle et al., ibid. 35, 1567 (1996). Isoln and structural studies of 39 natural epothilone variants: I. H. Hardt et al., J. Nat. Prod. 64, 847 (2001). Isoln and crystallization of D: R. L. Arslanian et al., ibid. 65, 570 (2002). Effects of A and B on microtubule proteins in comparison with paclitaxel: R. J. Kowalski et al., J. Biol. Chem. 272, 2534 (1997). Review of properties and clinical potential: D. M. Bollag, Expert. Opin. Invest. Drugs 6, 867-873 (1997); of biology, chemistry and therapeutic potential: K. C. Nicolaou et al., Angew. Chem. Int. Ed. 37, 2014-2045 (1998); idem et al., Chem. Commun. 2001, 1523-1535.
 
Derivative Type: Epothilone A
CAS Registry Number: 152044-53-6
CAS Name: (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-8,8,10,12-tetramethyl-3-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
Molecular Formula: C26H39NO6S
Molecular Weight: 493.66
Percent Composition: C 63.26%, H 7.96%, N 2.84%, O 19.45%, S 6.50%
Properties: Colorless crystals from ethyl acetate/toluene, mp 95°. Soly at 20° (g/l): water 0.7. uv max (methanol): 211, 249 nm (e 17800, 12500). [a]D21 -47.1° (c = 1.0 in methanol).
Melting point: mp 95°
Optical Rotation: [a]D21 -47.1° (c = 1.0 in methanol)
Absorption maximum: uv max (methanol): 211, 249 nm (e 17800, 12500)
 
Derivative Type: Epothilone B
CAS Registry Number: 152044-54-7
Additional Names: Patupilone
Manufacturers' Codes: EPO-906
Molecular Formula: C27H41NO6S
Molecular Weight: 507.68
Percent Composition: C 63.88%, H 8.14%, N 2.76%, O 18.91%, S 6.32%
Properties: Colorless crystals from ethyl acetate, mp 93-94°. uv max (methanol): 211, 249 nm (e 18600, 14100). [a]D21 -35° (c = 0.7 in methanol).
Melting point: mp 93-94°
Optical Rotation: [a]D21 -35° (c = 0.7 in methanol)
Absorption maximum: uv max (methanol): 211, 249 nm (e 18600, 14100)
 
Derivative Type: Epothilone D
CAS Registry Number: 189453-10-9
CAS Name: (4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-16-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]oxacyclohexadec-13-ene-2,6-dione
Additional Names: desoxyepothilone B
Manufacturers' Codes: KOS-862
Molecular Formula: C27H41NO5S
Molecular Weight: 491.68
Percent Composition: C 65.96%, H 8.40%, N 2.85%, O 16.27%, S 6.52%
Properties: Colorless crystals from ethanol + water, mp 120-121° (Arslanian). Also reported as colorless amorphous solid. [a]D22 -61.3° (c = 2.5 in methanol). uv max (methanol): 210, 248 nm (e 18400, 13200) (Hardt).
Melting point: mp 120-121° (Arslanian)
Optical Rotation: [a]D22 -61.3° (c = 2.5 in methanol)
Absorption maximum: uv max (methanol): 210, 248 nm (e 18400, 13200) (Hardt)

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