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A convenient and practical synthesis of 6-carboalkoxy-13-cycloalkyl-5 H -indolo[2,1- a ][2]benzazepine-10-carboxylic acid derivatives ( 6 ) has been developed. The key step in the synthesis utilizes an intramolecular tandem reaction sequence of a Michael addition followed by a Horner–Wadsworth–Emmons (HWE) olefination reaction between hemi-aminal 11 and methyl 2-(dimethoxyphosphoryl)acrylate 12 . The ring construction occurred efficiently and purification of the products 6 was straightforward. The C-10 methyl ester of 6a was hydrolyzed selectively to the carboxylic acid 13 while the olefin of 6d was converted to the cyclopropane 14 using trimethylsulfoxonium iodide in DMSO in the presence of NaH.

An efficient, one-pot Friedel–Crafts acylation/hydrolysis reaction promoted by the acidic ionic liquid 1-ethyl-3-methylimidazolium chloroaluminate (generated from 1-ethyl-3-methylimidazolium chloride (EmimCl) and aluminum chloride (X(AlCl3), mole fraction X = 0.75) for the formation of 3-glyoxylic acid derivatives of electron-deficient, substituted 4- and 6-azaindoles is described.

Aryl aminoacetonitriles are oxidized by NiO 2 –H 2 O or MnO 2 in the presence of a wide range of NH 2 -containing compounds to afford aryl amidines, presumably via iminium intermediates. A ‘one-pot’ procedure for the preparation of heteroaryl amidines from N -containing heteroaryl halides through a process comprising sequential S N Ar substitution and oxidation has also been developed.

A convenient and efficient one step, base-catalyzed synthesis of 3,5-disubstituted 1,2,4-triazoles by the condensation of a nitrile and a hydrazide is presented. A diverse range of functionality and heterocycles are tolerated under the reaction conditions developed, and the reactivity of the nitrile partner is relatively insensitive to electronic effects.

The synthetic transposition of the 7-hydroxyl group of paclitaxel to the 6-position is described. The route presented prepares both the 6-α- and β-isomers stereospecifically. The key step of this transposition involves the stereoselective reduction of the 6,7-α-thiocarbonate using tributylgermanium hydride.

An esperamicin core analog 4 with an epoxide trigger like that found in the related enediyne, dynemicin, was prepared. Surprisingly, it was found to be relatively stable; the p -aminophenyl substituent did not facilitate epoxide solvolysis to the extent that had been anticipated. A mild acid, pyridinium p -toluenesulfonate, was found to induce solvolysis of 4 and led to the formation of the cycloaromatized product 25 .

An enediyne analog ( 2 , R=H) that is a hybrid of the core structures of esperamicin and dynemicin was prepared. The key step in its synthesis was a Reissert-type reaction that involved intramolecular addition of the anion of a Z-1,3-diyn-2-ene to an N-acyl tetrahydrophenathridinium intermediate. It was found that 2 (R=H) readily undergoes epoxide rearrangement to an allylic alcohol ( 16 ). Both 2 (R=H) and 16 form the same cycloaromatized product 17 when heated in MeOH at 45 °C.

Synthesis and cytotoxicity properties of novel C-2′ analogues of paclitaxel are described. The analogues were synthesized using Holton's β-lactam approach to append the side chain on baccatin III. The key intermediate to the synthesis of novel analogues was prepared employing an unprecedented stereocontrolled addition of Grignard reagent to a chiral azetidine-2,3-dione.

Malononitrile could be utilized as a synthon for the carbonyl moiety via a one-pot process that was initiated via base-mediated S N Ar substitution of a heteroaryl halide. Subsequent peracetic acid oxidation of the resultant anion delivered an electrophilic acyl nitrile in situ that readily reacted with added nucleophiles to afford heteroaryl carboxylic acid derivatives. The reaction of the sodium salt of malononitrile with a series of heteroaryl chlorides followed by the subsequent addition of an amine and peracetic acid provided the corresponding heteroaryl amides.

A chemoselective approach to functionalize the C-10 position of 10-deacetyl baccatin III, a key intermediate for the semi-synthesis of paclitaxel, is described. The chemistry provides an easy access to a variety of C-10 hydroxyl derivatives, such as, ethers, esters, carbonates, carbamates, and sulfonates under mild conditions. The C-10 modified baccatin derivatives were further employed in the synthesis of novel biologically active Taxol® analogues.

The stable 12-β-hydroxybicyclo[7.1.0] diynene core 15 has been prepared stereospecifically. The key step consists of conjugate addition of dimethylaluminum benzenethiolate to enone aldehyde 12 followed by an in situ titanium isopropoxide assisted aldol cyclization to produce alcohol 13 as a single isomer.

The stereospecific synthesis of 6-α-hydroxy paclitaxel 10 , the major human metabolite of paclitaxel, is described. The 6,7-α-diol 4 , obtained from paclitaxel, is converted to the 6,7-β-cyclic sulfate followed by nitrate addition and reduction to afford the title compound.

The Stereochemistry of C-6,7 epoxy paclitaxel was determined by single crystal X-ray analysis of the baccatin derivative to be 6α, 7α. Thus finding corrects the structure reported by Kingston et al based on NOE data and corrects the discrepancy reported for facial selectivity of the reaction of osmium tetroxide and dimethyldioxirane with the C-6,7 olefin of paclitaxel.

Fused cyclopropanes including 3-carene and isosequicarene have been prepared by treatment of γ-stannyl alcohols with thionyl chloride.

A novel chemical sequence for the conversion of a lactone antitumor agent 1 (etoposide) to the corresponding lactam 2 is described. The key steps involve a Mitsunobu cyclization (Ph 3 P, DEAD) of the -hydroxymethyl acyl benzaldehyde hydrazone 6 to a lactam derivative 7 followed by reductive cleavage (RaNi) to lactam 2 .

The diynene lithium acetylide 5 adds to 2-siloxy-2-cyclohexenone 6 followed by silyl migration to produce ketone adduct 7 , an intermediate towards a simple Esperamicin core