Design, synthesis, and biological evaluation of artemisinin-indoloquinoline hybrids as potent antiproliferative agents.

A series of artemisinin-indoloquinoline hybrids were designed and synthesized in an attempt to develop potent and selective anti-tumor agents. Compounds 7a-7f, 8 and 9 were prepared and characterized. Their antiproliferative activities against MV4-11, HCT-116, A549, and BALB/3T3 cell lines in vitro were tested.

Cyclopentanoids from cyclopentadiene: synthesis of (-)-methyl jasmonate and (+)-12-oxophytodienoic acid.

Linoleic acid metabolites, (-)-methyl jasmonate and (+)-12-oxophytodienoic acid ((+)-12-oxo-PDA), were prepared from the same precursor (1,2-trans, 1,3-cis, 2'Z)-2-(pent-2'-enyl)-cyclopent-4-en-1,3-diol, which was obtained by regioselective pent-2-enylation of cyclopentadiene and following photooxidation to cis-1,3-diol. A methoxycarbonylmethyl substituent was introduced to the cyclopentane ring via alkylation of the pi-allyl palladium intermediate derived from (1R,2S,3S,2'Z)-3-acetoxy-2-(pent-2'-enyl)cyclopent-4-ene-1-ol with dimethyl malonate for (-)-methyl jasmonate. The alpha-chain was introduced to the cyclopentane ring via the S(N)2 type nucleophilic substitution of (1S,2R,3R,2'Z)-3-acetoxy-2-(pent-2'-enyl)cyclopent-4-ene-1-ol with a dialkylcuprate for (+)-12-oxo-PDA.

Regioselective ring opening of benzylidene acetal protecting group(s) of hexopyranoside derivatives by DIBAL-H.

The reductive ring-opening reaction of benzylidene-protected glucosides and mannosides such as methyl 2,3-di-O-benzyl-4,6-O-benzylidene-alpha-d-glucoside (1) and methyl 2,3-di-O-benzyl-4,6-O-benzylidene-alpha-d-mannoside (4) by using a toluene stock solution of DIBAL-H and a dichloromethane stock solution of DIBAL-H gives mainly or selectively the corresponding 2,3,4-tri-O-benzyl derivatives (2, 5) and 2,3,6-tri-O-benzyl derivatives (3, 6), respectively, although that of methyl 2,3-di-O-benzyl-4,6-O-benzylidene-alpha-d-galactoside (7) gives methyl 2,3,6-tri-O-benzyl-alpha-d-galactoside (9) selectively irrespective of the solvent of the stock solution of DIBAL-H. Similarly, the reaction of the exo-isomer of methyl 2,3:4,6-di-O-benzylidene-alpha-d-mannopyranosides (exo-10) with a toluene stock solution and dichloromethane stock solutions of DIBAL-H selectively gives methyl 3-O-benzyl-4,6-O-benzylidene-alpha-d-mannoside (12) and methyl 2-O-benzyl-4,6-O-benzylidene-alpha-d-mannoside (11), respectively, although that of endo-10 selectively affords 11, irrespective of the solvent of the stock solution of DIBAL-H.

Stereoselective 4-benzyloxybut-2-enylation of aldehydes via an allyl-transfer reaction using a chiral allyl donor.

[reaction: see text] A direct and highly stereoselective (E)-4-benzyloxybut-2-enylation of aldehydes was successfully carried out to give 5-benzyloxyhomoallylic alcohol (11) via an allyl-transfer reaction using a chiral allyl donor (10). The chiral allyl donor (10) was prepared by catalytic Sharpless asymmetric epoxidation of 3-methylbut-2-en-1-ol, followed by a stereospecific vinyl Grignard reaction of the epoxide in the presence of CuBr and selective benzylation of the primary alcohol of diol.

Reactivity of N-alkanoyloxy-2,2,6,6-tetramethylpiperidines (O-acylTEMPOs) towards hydride-transferring or metallic alkylating reagents; unprecedented stability and application to chemoselective transformations.

Owing to the unprecedented stability of O-acylTEMPOs towards hydride-transferring and metallic alkylating reagents such as LiAlH4 and RMgX, chemoselective transformation of diacid mixed alkyl/TEMP-1-yl esters, where O-acylTEMPOs remained intact, is achieved with these reagents, giving the corresponding carbinols, respectively.

A novel enantioselective (2Z)-alk-2-enylation of aldehydes via an allyl-transfer reaction from chiral allyl donors prepared from (+)-isomenthone.

A highly enantioselective (2Z)-alk-2-enylation of aldehydes was successfully achieved by an allyl-transfer reaction from a chiral allyl donor, which was easily obtained by separation of a diastereomeric mixture of the corresponding homoallylic alcohol gamma-adducts derived from (+)-isomenthone with alk-2-enylmagnesium chloride. [reaction: see text]