145362-83-0Relevant academic research and scientific papers
Development of aliphatic alcohols as nucleophiles for palladium-catalyzed DYKAT reactions: Total synthesis of (+)-hippospongic acid A
Trost, Barry M.,Machacek, Michelle R.,Tsui, Hong C.
, p. 7014 - 7024 (2007/10/03)
The ability to use aliphatic alcohols as competent nucleophiles in the palladium-catalyzed dynamic kinetic asymmetric transformation of Baylis-Hillman adducts is explored. High yield and enantioselectivity is obtained for both the kinetic transformation a
Polyene substrates with unusual methylation patterns to probe the active sites of three catalytic antibodies
Kim, Geun Tae,Wenz, Marion,Park, Jong Il,Hasserodt, Jens,Janda, Kim D
, p. 1249 - 1262 (2007/10/03)
The synthesis of two tetraenes that differ in their methylation pattern from the natural substrate in lanosterol biosynthesis, 2,3-oxidosqualene, and their examination with three catalytic antibodies is described. The design of these novel, linear terpenoid structures was governed by initial results obtained from the characterization of the three catalytic antibodies. These were generated by immunization with a steroidal hapten that mimics multicyclization without the necessity for anti-Markovnikov additions or ring expansions. Such a reaction cascade would represent a more 'primitive' version compared to the oxidosqualene cyclization observed in lanosterol, cycloartenol and β-amyrin biosynthesis and would not require a tail-to-tail connection of the third and fourth isoprene unit as seen in squalene. The first tetraene design (A) only contains trisubstituted double bonds and hence its synthesis starts from farnesol and tris-norgeraniol. The second tetraene design (B) is considered the more precise match to the inducing hapten that generated the antibody collections by exhibiting one disubstituted double bond and its synthesis utilizes a tris-norgeraniol derivative and a symmetrical bis-allylic alcohol as key building blocks. Chromatographic comparison studies lead to the conclusion that the currently studied antibodies also produce monocyclic products from the two substrates as has been formerly observed with a squalene-derived substrate. In contrast, 2,3-oxidosqualene is not accepted by these catalysts supporting the notion that the current substrates are fully bound by recognition of both terminal functional groups.
Synthesis of Vinyl Sulfide Analogs of 2,3-Oxidosqualene and Their Inhibition of 2,3-Oxidosqualene Lanosterol-Cyclases
Zheng, Yi Feng,Dodd, Dharmpal S.,Oehlschlager, Allan C.,Hartman, Peter G.
, p. 5255 - 5276 (2007/10/02)
Syntheses of all trans(6E)-5-, (10E)-9-, (14E)-16- and (18E)-20-thia-2,3-oxidosqualenes as inhibitors of 2,3-oxidosqualene-lanosterol cyclase (OSC) are reported.To mimic the natural geometry of 2,3-oxidosqualene (2,3-OS), we required E-vinyl sulfides which were prepared by condensation of sulfur-substituted Wittig-Horner reagents (α-thioterpenoidyl diphenylphosphine oxides) with appropriate aldehydes.Mixtures of syn and anti α-hydroxydiphenylphosphine adducts were seperated by chromatography and the syn isomers were transformed to the E-vinyl sulfides.Both (6E)-5- and (18E)-20-thia-2,3-OS inhibited OSC from Candida albicans (IC50 = 47 and 0.2 μM, respectively) and rat liver (IC50 = 7.7 and 0.32 μM, respectively).Their activities were compared with those of previously synthesized (6E)-8- and (14E)-13-thia-2,3-Oss (IC50 = 0.68 and 45 μM, C. albicans, IC50 = 34 and 61 μM, rat liver, respectively).The best inhibitor among these compounds for the OSC of C. albicans and rat liver is the (18E)-20-thia-2,3-OS.This result suggests that modification of C-20 region of the 2,3-OS skeleton is an attractive strategy for development of OSC inhibitors.
