Whole-cell biooxidation of bromobenzene with Pseudomonas putida 39D or the recombinant Escherichia coli JM109 (pDTG601) yields (1S,2S)-3-bromocyclohexa-3,5-diene-1,2-diol (9a), which is protected as the acetonide and converted to vinylaziridines 7, 15a, 63, and 64. Our route to (+)-pancratistatin features the coupling of a higher order cyanocuprate (derived by ortho-metalation from N,N-dimethyl-2-[(tert-butyldimethylsilyl)oxy]-3,4-(methylenedioxy)benzamide) with aziridine 7 to generate 28, which contains the carbon framework of the title alkaloid. Functional group manipulations resulted in the preparation of epoxydiol 50, which was transformed in a unique fashion and under mild conditions (H2O/PhCO2Na) to (+)-pancratistatin, thus completing a concise synthesis of (+)-pancratistatin in 14 steps from bromobenzene (2% overall yield). To improve this first generation attempt, a new route was devised utilizing carbomethoxyaziridine 64 and its coupling to the cuprate of 3,4-(methylenedioxy)bromobenzene. The add...

Toluene Dioxygenase-Mediated cis-Dihydroxylation of Aromatics in Enantioselective Synthesis. Asymmetric Total Syntheses of Pancratistatin and 7-Deoxypancratistatin, Promising Antitumor Agents1

Enantioselective total syntheses of the antitumor alkaloids, (+)-narciclasine and (+)-pancratistatin, are reported. These syntheses feature a stereo- and regiocontrolled aryl enamide photocyclization to construct a common, advanced intermediate possessing a trans-fused BC substructure. Differential functional group interchange in the C-ring of this phenanthridone core structure allows for the production of the two target natural products in enantiomerically pure form.

Studies on the narciclasine alkaloids: Total synthesis of (+)- narciclasine and (+)-pancratistatin

The synthesis of isocoumarins over the last decade. a review

Methods published over the last 10 years for the production of substituted 1(2H)-isoquinolones, including those involving the use of organometallic compounds, are discussed.

Synthesis of 1(2H)-Isoquinolones. (Review)

Organocerium compounds in synthesis

A convergent, asymmetric approach to the antitumor alkaloid pancrastistatin, based on a novel annulative construction of the highly oxygenated phenanthridone system is described

An annulative, carbohydrate-based approach to pancratistatin and structurally related phenanthridone alkaloids. Synthesis of (+)-tetrabenzyllycoricidine

A procedure is described for the conversion of 3-bromo-2-cyclohexenone into the functionalised bicyclic oxetanes 13a and 13b, 7-oxabicyclo[4.2.0]octene derivatives. These heterocycles undergo halogen-metal exchange readily in the presence of tert-butyllithium at -78 o C, and the resulting vinyl anions are capable of nucleophilic addition to ketones either directly or via cerate intermediates without complication. Whereas 2-(7-oxabicyclo[4.2.0]oct-2-en-3-yl)-5-norbornen-2-ol 20 smoothly undergoes anionic oxy-Cope rearrangement at 0 o C when transformed into its potassium salt, alcohols 23 and 24, 2-(7-oxabicyclo[4.2.0]oct-2-en-3-yl)-1-vinyl-norbornan-2-ol are especially prone to aromatisation with loss of the oxetane subunit under the same conditions. In order to skirt these complications, attention was directed to bromo acetonides 1,3-benzodioxan derivatives 36 and 37. Sequential treatment of 36 with tert-butyllithium and anhydrous cerium trichloride gave the corresponding organocerate that added stereoselectively to the endo surface of the carbonyl group in optically pure ketone 7,7-dimethyl-1-vinyl-norbornan-2 -one 22. The individual diastereomers thus produced were subjected to anionic oxy-Cope rearrangement in the presence of hexamethyldisilazide and air to give methanocyclodeca[f]-1,3-benzodioxine derivative

Synthetic equivalents of the taxol C,D ring system. Examination of nucleophilic bicyclic oxetanes and less-strained acetonide equivalents

Several optically pure cis-tricyclo[9.3.1.0 3,8 ]pentadecanones have been prepared via anionic oxy-Cope rearrangement of exo-norbornanol precursors that have been obtained by convergent coupling of two functionalized reaction partners. The sigmatropic rearrangement is shown to proceed with exceptionally good stereochemical transmission because of universal adherence to the same endochair transition state. The atropisomeric aspects of this pivotal transformation are addressed. Also investigated was the proclivity of the products to undergo transannular hemiketal formation following osmylation of the bridgehead double bond. As matters turn out, the operation or nonoperation of this intramolecular addition to the C-9 carbonyl group is amenable to control merely by adjusting properly the stereochemistry of a single pendant substituent

Richard C. Thompson

Papers

An annulative, carbohydrate-based approach to pancratistatin and structurally related phenanthridone alkaloids. Synthesis of (+)-tetrabenzyllycoricidine

Synthetic equivalents of the taxol C,D ring system. Examination of nucleophilic bicyclic oxetanes and less-strained acetonide equivalents

A means for stereocontrolled introduction of the C-2 oxygen substituent in functionalized cis-tricyclo[9.3.1.03,8]pentadecanones related to taxol

Dehydrogenation of Alcohols by Lithium Metal-Ethylenediamine System

A Means for Stereocontrolled Introduction of the C‐2 Oxygen Substituent in Functionalized cis‐Tricyclo(9.3.1.03,8)pentadecanones Related to Taxol.