174810-40-3Relevant academic research and scientific papers
A concise synthesis of the naphthoic acid component of neocarzinostatin chromophore featuring a new photocyclization reaction
Myers, Andrew G.,Subramanian, Vijaya,Hammond, Marlys
, p. 587 - 590 (1996)
A 6-step synthesis of the naphthoic acid component of the natural antitumor agent neocarzinostatin chromophore is described. The synthetic route employs 4-bromo-3-methylanisole as the starting material, proceeds in 31-37% yield for the 6 steps, and featur
Rhodium-catalyzed heck-type coupling of boronic acids with activated alkenes in an aqueous emulsion
Lautens, Mark,Mancuso, John,Grover, Harpreet
, p. 2006 - 2014 (2007/10/03)
Intermolecular couplings between arylboronic acids and activated alkenes catalyzed by a water-soluble tert-bulyl amphosrhodium complex were found to progress at room temperature and generated Heck-type products with high yields and excellent selectivity. Substitution on the alkene component encouraged the formation of products arising from a conjugate addition-protonation process. In the case of Heck product formation, it was necessary to add two equivalents of the alkene component whereby one equivalent is believed to act as a sacrificial hydride acceptor.
Synthesis of analogues of calicheamicin and neocarzinostatin chromophore
Cirla, Alessandra,McHale, Angela R.,Mann, John
, p. 4019 - 4029 (2007/10/03)
The work presents a synthetic route to the CD ring of calicheamicin and in the case of neocarzinostatin an approach to a functionalised cyclopentane-1,3-diol containing the naturally occurring naphthoate and a glucosamine motif. In the case of the NCS derivative some biological activity (cytotoxicity) was observed.
Imidazolylidene carbene ligated palladium catalysis of the Heck reaction in the presence of air.
Liu, Jingping,Zhao, Yuanhong,Zhou, Yongyun,Li, Liang,Zhang, Tony Y,Zhang, Hongbin
, p. 3227 - 3231 (2007/10/03)
Five 1,3-disubstituted imidazolium salts were synthesized. Their Heck reaction activities were evaluated. A convenient, efficient and high yielding procedure based on these compounds for the arylation of olefins was developed. Heck reactions mediated by these palladium-N-heterocyclic carbene complexes were conducted under air and even in the presence of several common oxidants.
Development of an enantioselective synthetic route to neocarzinostatin chromophore and its use for multiple radioisotopic incorporation
Myers, Andrew G.,Glatthar, Ralf,Hammond, Marlys,Harrington, Philip M.,Kuo, Elaine Y.,Liang, Jun,Schaus, Scott E.,Wu, Yusheng,Xiang, Jia-Ning
, p. 5380 - 5401 (2007/10/03)
A convergent, enantioselective synthetic route to the natural product neocarzinostatin chromophore (1) is described. Synthesis of the chromophore aglycon (2) was targeted initially. Chemistry previously developed for the synthesis of a neocarzinostatin core model (4) failed in the requisite 1,3-transposition of an allylic silyl ether when applied toward the preparation of 2 with use of the more highly oxygenated substrates 27 and 54. An alternative synthetic plan was therefore developed, based upon a proposed reduction of the epoxy alcohol 58 to form the aglycon 2, a transformation that was achieved in a novel manner, using a combination of the reagents triphenylphosphine, iodine, and imidazole. The successful route to 1 and 2 began with the convergent coupling of the epoxydiyne 15, obtained in 9 steps (43% overall yield) from D-glyceraldehyde acetonide, and the cyclopentenone (+)-14, prepared in one step (75-85% yield) from the prostaglandin intermediate (+)-16, affording the alcohol 22 in 80% yield and with 20:1 diastereoselectivity. The alcohol 22 was then converted into the epoxy alcohol 58 in 17 steps with an average yield of 92% and an overall yield of 22%. Key features of this sequence include the diastereoselective Sharpless asymmetric epoxidation of allylic alcohol 81 (98% yield); intramolecular acetylide addition within the epoxy aldehyde 82, using Masamune's lithium diphenyltetramethyldisilazide base (85% yield); selective esterification of the diol 84 with the naphthoic acid 13 followed by selective cleavage of the chloroacetate protective group in situ to furnish the naphthoic acid ester 85 in 80% yield; and elimination of the tertiary hydroxyl group within intermediate 88 using the Martin sulfurane reagent (79% yield). Reductive transposition of the product epoxy alcohol (58) then formed neocarzinostatin chromophore aglycon (2, 71% yield). Studies directed toward the glycosylation of 2 focused initially on the preparation of the N-methylamino → hydroxyl replacement analogue 3, an α-D-fucose derivative of neocarzinostatin chromophore, formed in 42% yield by a two-step Schmidt glycosylation-deprotection sequence. For the synthesis of 1, an extensive search for a suitable 2′-N- methylfucosamine glycosyl donor led to the discovery that the reaction of 2 with the trichloroacetimidate 108, containing a free N-methylamino group, formed the α-glycoside 114 selectively in the presence of boron trifluoride diethyl etherate. Subsequent deprotection of 114 under mildly acidic conditions then furnished the labile chromophore (1). The synthetic route was readily modified for the preparation of singly and doubly 3H- and 14C -labeled 1, compounds unavailable by other means, for studies of the mechanism of action of neocarzinostatin in vivo.
