100606-34-6Relevant articles and documents
ANTI-HIV COMPOUNDS
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Paragraph 0312, (2016/07/05)
This invention provides, among other things, tetrahydroisoquinolines useful for treating viral infections, pharmaceutical formulations containing such compounds, as well as methods of inhibiting the replication of a virus, such as HIV, or treating a disease, such as AIDS.
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.
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 (2007/10/02)
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
Synthesis of Substituted 1,2-Dihydroisoquinolines by the Intramolecular 1,3-Dipolar Alkyl Azide-Olefin Cycloaddition
Liu, Jia-Ming,Young, Jenn-Jong,Li, Yu-Jang,Sha, Chin-Kang
, p. 1120 - 1123 (2007/10/02)
A general synthesis of substituted 1,2-dihydroisoquinolines based on intramolecular 1,3-dipolar cycloaddition of alkyl azides and olefins is described.Reaction of bromide 4 with sodium azide afforded azide 5, which underwent 1,3-dipolar cycloaddition intramolecularly to give triazoline 6 .Rearrangement of triazoline 6 on silica gel gave diazo compound 7.Treatment of 7 with rhodium acetate afforded substituted 1,2-dihydroisoquinoline 9 in good overall yield.
Organoiron Complexes in Organic Synthesis. Part 27. Synthesis and Reactivity of Tricarbonyliron Derivatives of 1,2-Disubstituted 4-Alkoxycyclohexadienylium Cations
Pearson, Anthony J.,Perrior, Trevor R.,Griffin, David A.
, p. 625 - 631 (2007/10/02)
The synthesis, and reactions with stable enolate nucleophiles, of 1,2-disubstituted 4-alkoxycyclohexadienylium(tricarbonyl)iron complexes (3a), (3b), (3c), and (3d) is described.Only the 1,2-dimethyl-4-isopropoxycyclohexadienylium complex (3b) was found to react with nucleophiles with sufficiently high regioselectivity to allow a useful method of preparation of 3,4,4-trisubstituted cyclohexenones.
