Corticosteroid Decomposition via a Mixed Anhydride

Abstract

Oxidation of dexamethasone in an aqueous suspension by air during prolonged storage produces the 17alpha-formyloxy-17beta-carboxylic acid 4. A pathway to 4 is proposed that involves Baeyer-Villiger-type oxidation of keto aldehyde 1 to mixed anhydride 5, followed by intramolecular formyl transfer. Synthetically, acid 3 was reacted with N,N'-carbonyldiimidazole followed by triethylammonium formate in order to generate the transient anhydride 5 en route to an authentic sample of 4.

Koenigs–Knorr Glycosylation Reaction Catalyzed by Trimethylsilyl Trifluoromethanesulfonate

“…Under classical Koenigs-Knorr reaction conditions, [2][3][4] ag lycosyl bromide( or chloride) donor is coupled with ag lycosyl acceptor(alcohol, ROH)i nt he presence of silver oxide (or carbonate).T his reaction is slow, and even glycosidations of reactive, perbenzylated donors require many hours( or even days) to produce the respective glycoside products.T his reaction is particularly sluggish with less reactive perbenzoylated bromides. To advance the classical Koenigs-Knorr glycosylation, many activators including salts of mercury, [5][6][7][8] cadmium, [9][10][11] tin, [12,13] zinc, [14,15] indium, [16,17] silver [18][19][20][21][22][23][24][25][26] have emerged. [27] Nevertheless, these modifications failed to adequately enhance the reactiont hat continued to suffer from fair yields, poor reactivity of donors, substrate scope, and the requirement to use excess of toxic or expensive reagents.T his prompted the investigationo fo ther,n on-metallic activators andp romoters including halide ions, [28] iodine or IBr with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone/1,4-diazobicyclo[2.2.2]octane( DDQ/DABCO), [29,30] bromine, [31] and 3,3-difluoroxindole (HOFox), [32,33] diarylborinic acid, [34] iodonium ions, [35] halogen bonding, [36] supercriticalC O 2 , [37] and organocatalysis.…”

Recent Advances in the Analysis of Steroid Hormones and Related Drugs

“…244 Of the other corticosteroids several synthesis-related impurities and degradants were identified in dexamethasone. 245,246 Of these, the 17β-carboxy-17α-formyloxy derivative forming under storage conditions via a mixed anhydride is especially interesting. 246 The structure elucidation of impurities in fluticasone propionate (among others an interesting -S-S-bridged dimer) is a good example for the application of new techniques such as CEC-MS 228 and on-line HPLC-NMR.…”

“…245,246 Of these, the 17β-carboxy-17α-formyloxy derivative forming under storage conditions via a mixed anhydride is especially interesting. 246 The structure elucidation of impurities in fluticasone propionate (among others an interesting -S-S-bridged dimer) is a good example for the application of new techniques such as CEC-MS 228 and on-line HPLC-NMR. 247 The light-induced degradation of methylprednisolone suleptamate lead to interesting, unpredictable structures.…”

The effect of calcium hydroxide on the steroid component of Ledermix® and Odontopaste®

“…Whether this remains the case with the tritium-labelled triamcinolone acetonide is unknown. Previous studies have found varying degrees of breakdown of steroids at high pH (Dekker & Buijs 1980, Hansen & Bundgaard 1980, Ogata et al 1998, Spangler & Mularz 2001, Conrow et al 2002, Teng et al 2003, Nygaard et al 2004, Görög 2010), so it is conceivable that the tritium labelling may not be on an active molecule, but may be on a breakdown product.…”

“…Whether this remains the case with the tritiumlabelled triamcinolone acetonide is unknown. Previous studies have found varying degrees of breakdown of steroids at high pH (Dekker & Buijs 1980, Hansen & Bundgaard 1980, Ogata et al 1998, Spangler & Mularz 2001, Conrow et al 2002, Teng et al 2003, Nygaard et al 2004, Görög 2010, so it is conceivable that the tritium labelling may not be on an active molecule, but may be on a breakdown product. Therefore, this study was undertaken to investigate the effects of the addition of calcium hydroxide in the form of calcium hydroxide powder and in the form of Pulpdent Ò Paste (Pulpdent Corporation, Watertown, MA, USA) on the stability of the steroid component of two endodontic pastes, Odontopaste Ò (Australian Dental Manufacturing) and Ledermix Ò (Haupt Pharma GmbH).…”