1.Clindamycin hydrochloride monohydrate and its ethanol solvate.
Ravikumar K1, Sridhar B. Acta Crystallogr C. 2010 Feb;66(Pt 2):o97-100. doi: 10.1107/S0108270110000958. Epub 2010 Jan 22.
Clindamycin hydrochloride, an antibiotic of the lincomycin family, was crystallized as the monohydrate, namely (2S,4R)-2-(N-{(1S,2S)-2-chloro-1-[(3R,4S,5R,6R)-3,4,5-trihydroxy-6-(methylsulfanyl)perhydropyran-2-yl]propyl}aminocarbonyl)-4-propylpyrrolidinium chloride monohydrate, C(18)H(34)ClN(2)O(5)S(+).Cl(-).H(2)O, (I), and as the monohydrate ethanol solvate, C(18)H(34)ClN(2)O(5)S(+).Cl(-).H(2)O.C(2)H(6)O, (II). The conformation of the clindamycin molecule in both crystal structures is the same and is found to be similar to that in enzyme-bound clindamycin. The simultaneous presence of free chloride ions and water molecules in (I) and of additional ethanol molecules in (II) provides an interesting network of hydrogen bonds. The significance of this study lies in the interactions in these structures and the aggregations occurring via hydrogen bonds in the hydrated and solvated crystalline forms of the title compound.
2.Development and validation of a liquid chromatography-ultraviolet absorbance detection assay using derivatisation for the novel marine anticancer agent ES-285 x HCl [(2S,3R)-2-amino-3-octadecanol hydrochloride] and its pharmaceutical dosage form.
den Brok MW1, Nuijen B, Miranda E, Floriano P, Munt S, Manzanares I, Beijnen JH. J Chromatogr A. 2003 Dec 12;1020(2):251-8.
ES-285 x HCl [(2S,3R)-2-amino-3-octadecanol hydrochloride] is a novel investigational anticancer agent, which has shown in vitro and in vivo cytotoxic activity against various tumor cell lines with selectivity for certain solid tumors. The pharmaceutical development of ES-285 x HCl warranted the availability of an assay for the quantification and purity determination of ES-285 x HCl active pharmaceutical ingredient (API) and its pharmaceutical dosage form. A liquid chromatographic method (LC) comprising of derivatisation of ES-285 x HCl with phenylisothiocyanate and UV-detection was developed. The method was found to be linear, precise and accurate. The assay also proved selectivity as determined by analysing ES-285 x HCl in combination with 15 analogues and in combination with hydroxypropyl-beta-cyclodextrin, the excipient used in the lyophilised pharmaceutical dosage form. Stress testing showed that the degradation products were separated from the parent compound, confirming its stability indicating capacity.
3.Asymmetric synthesis of (1R,2S,3R)-3-methylcispentacin and (1S,2S,3R)-3-methyltranspentacin by kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate.
Bunnage ME1, Chippindale AM, Davies SG, Parkin RM, Smith AD, Withey JM. Org Biomol Chem. 2003 Nov 7;1(21):3698-707.
Conjugate addition of lithium dibenzylamide to tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate occurs with high levels of stereocontrol, with preferential addition of lithium dibenzylamide to the face of the cyclic alpha,beta-unsaturated acceptor anti- to the 3-methyl substituent. High levels of enantiorecognition are observed between tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate and an excess of lithium (+/-)-N-benzyl-N-alpha-methylbenzylamide (10 eq.) (E > 140) in their mutual kinetic resolution, while the kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate with lithium (S)-N-benzyl-N-alpha-methylbenzylamide proceeds to give, at 51% conversion, tert-butyl (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate consistent with E > 130, and in 39% yield and 99 +/- 0.5% de after purification. Subsequent deprotection by hydrogenolysis and ester hydrolysis gives (1R,2S,3R)-3-methylcispentacin in > 98% de and 98 +/- 1% ee.
