Stieglitz rearrangement of N,N-dichloro-beta,beta-disubstituted taurines under mild aqueous conditions.
New topical anti-infectives comprised of N,N-dichloro-beta,beta-disubstituted taurines [Tetrahedron Lett.2008, 49, 2193; Biorg. Med. Chem. Lett. 2009, 19, 196] have been examined for structure-stability relationships (SSR) based upon various alkyl, heteroalkyl and cycloalkyl beta-substitutions. These substitutions affect order-of-magnitude changes in the aqueous stability of these N,N-dichloroamines which can undergo Stieglitz rearrangement of alkyl groups under extremely mild conditions (H(2)O, pH 4-7, 0-20 mM acetate or phosphate buffer, 20-40 degrees C). This process produces beta-ketosulfonic acids which function as substrates for chlorination by the N-chlorotaurines which leads to their further degradation.
Shiau
Timothy P
TP
NovaBay Pharmaceuticals, 5980 Horton St. Suite 550, Emeryville, CA 94608, USA. tshiau@novabaypharma.com
Houchin
Ashley
A
Nair
Satheesh
S
Xu
Ping
P
Low
Eddy
E
Najafi
Ramin Ron
RR
Jain
Rakesh
R
D020650:Combinatorial Chemistry Techniques; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013654:Taurine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014867:Water / Q000737:chemistry
D006843:Hydrocarbons, Chlorinated; D014867:Water; D013654:Taurine