| US 7,572,606 B1 | ||
| Biosyntheses of salinosporamide A and its analogs and related methods of making salinosporamide A and its analogs | ||
| Kin Sing Lam, San Diego, Calif. (US); Michael Palladino, Olivenhain, Calif. (US); and Ginger Tsueng, San Diego, Calif. (US) | ||
| Assigned to Nereus Pharmaceuticals, Inc., San Diego, Calif. (US) | ||
| Filed on Sep. 08, 2006, as Appl. No. 11/517,899. | ||
| Claims priority of provisional application 60/715404, filed on Sep. 09, 2005. | ||
| Claims priority of provisional application 60/816771, filed on Jun. 26, 2006. | ||
| Claims priority of provisional application 60/816753, filed on Jun. 26, 2006. | ||
| Int. Cl. C12P 17/18 (2006.01); A61K 31/047 (2006.01); C07D 491/044 (2006.01); C12P 41/00 (2006.01) | ||
| U.S. Cl. 435—119 [514/64; 514/412; 514/210.06; 514/421; 530/347; 548/453; 549/302; 435/280] | 18 Claims |
1. A method of producing a first compound of Formula I,
 wherein the dashed lines represent a single or a double bond, wherein R1 is separately selected from the group consisting of a hydrogen, a halogen, mono-substituted, poly-substituted or unsubstituted
variants of the following residues: saturated C1-C24 alkyl, unsaturated C2-C24 alkenyl or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl,
arylalkoxy carbonyl, alkoxy carbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, cycloalkylacyl, hydroxy,
alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, where n is equal
to 1 or 2, and if n is equal to 2, then R1 can be the same or different;
wherein R2 is selected from the group consisting of hydrogen, a halogen, mono-substituted, poly-substituted or unsubstituted variants
of the following residues: saturated C1-C24 alkyl, unsaturated C2-C24 alkenyl or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl,
arylalkoxy carbonyl, alkoxy carbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, cycloalkylacyl, hydroxy,
alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl;
wherein R3 is selected from the group consisting of a halogen, mono-substituted, poly-substituted or unsubstituted variants of the following
residues: saturated C1-C24 alkyl, unsaturated C2-C24 alkenyl or C2-C24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl,
arylalkoxy carbonyl, alkoxy carbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, cycloalkylacyl, hydroxy,
alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl;
wherein each of E1, E2, E3 and E4 is a substituted or unsubstituted heteroatom;
the method comprising culturing a strain of Salinospora in a saline medium using a feedstock that is deficient in or has an excess of one or more of proprionate, butyrate, or valerate
compared to levels of proprionate, butyrate, and valerate found in a medium comprising starch, Hy soy, and yeast in a ratio
of 10 g to 4 g to 4 g such that the relative yield of the first compound in comparison to the yield of a second compound of
Formula I is substantially different than the relative yield of the first compound in comparison to the yield of the second
compound obtained when the strain is cultured in a medium comprising starch, Hy soy, and yeast in a ratio of 10 g to 4 g to
4 g.
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