59320-77-3Relevant articles and documents
Aliphatic hydroxylation and epoxidation of capsaicin by cytochrome P450 CYP505X
Migglautsch, Anna K.,Willim, Melissa,Schweda, Bettina,Glieder, Anton,Breinbauer, Rolf,Winkler, Margit
, p. 6199 - 6204 (2018/09/21)
Microbial cytochrome P450 enzymes (CYPs) are able to mimic the metabolism of human CYPs. One challenge is to identify the respective drug metabolites and to compare substrate specificities to those of the human enzymes. In this study, a class VIII self-sufficient CYP from Aspergillus fumigatus (CYP505X) and variants of this enzyme were heterologously expressed in E. coli. The substrate scope of the variants was determined using active pharmaceutical ingredients (APIs) and (hetero)cyclic compounds. Capsaicin – the active compound in chili peppers – was oxidized most efficiently (4.36 μM/min) in a whole cell mediated biotransformation. The products were isolated, purified and their structures elucidated by 1D and 2D NMR. The two major metabolites showed modifications on the lipophilic side chain. Specifically, capsaicin was hydroxylated at position 8 to give (E)-8-hydroxy-N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide and epoxidized at the double bond to give N-(4-hydroxy-3-methoxybenzyl)-5-(3-isopropyloxiran-2-yl)-pentanamide.
A convenient transformation of 2-alkylidenecycloalkanones into alkyl-substituted bicyclo[ n.1.0]alkan-1-ols: Application to the synthesis of capsaicin
Kananovich, Dzmitry G.,Zubrytski, Dzmitry M.,Kulinkovich, Oleg G.
scheme or table, p. 1043 - 1046 (2010/06/14)
Treatment of 2-alkylidenecycloalkanones with hydrogen iodide in benzene and subsequent reaction of the obtained -iodo ketones with zinc dust in THF in the presence of chlorotrimethylsilane or titanium(IV) chlorotriisopropoxide led to exo- and endo-(n+3)-alkylbicyclo[n.1.0]alkan-1-ols in high yields. Cyclization of the intermediate -iodo ketones under these conditions proceeded in a moderate to good diastereoselectivity, and the resulted bicyclic cyclopropanols were easily separated by column chromatography over silica gel. exo-7- Isopropylbicyclo[4.1.0]heptan-1-ol obtained in this manner was efficiently employed as a key intermediate in the synthesis of capsaicin. Georg Thieme Verlag Stuttgart - New York.
A general and stereoselective synthesis of the capsaicinoids via the orthoester Claisen rearrangement
Kaga, Harumi,Goto, Kouhei,Takahashi, Tomiki,Hino, Masao,Tokuhashi, Takashi,Orito, Kazuhiko
, p. 8451 - 8470 (2007/10/03)
Capsaicin, a main pungent principle of hot pepper, and its 15 analogs have been efficiently synthesized. The key step of this synthetic scheme is the orthoester Claisen rearrangement, which transformed allylic alcohols 2A-C to (E)-alkenoates 3A-C (E/Z > 100) in a highly stereoselective manner. The subsequent carbon chain elongations on 3 based on the cyanation or the malonic acid ester synthesis afforded (E)-alkenoic acids 8, which were converted to the corresponding acid chloride and then coupled with vanillylamine to give capsaicinoids. HPLC and CE (capillary electrophoresis) analyses of these capsaicinoids were also carried out.
