Stanley Raucher

Sequence preferences of DNA interstrand cross-linking agents: Importance of minimal DNA structural reorganization in the cross-linking reactions of mechlorethamine, cisplatin and mitomycin C

Abstract Interstrand cross-linking of DNA is believed to account for the cytotoxicity of many bifunctional alkylating agents, some of which are useful in the treatment of human cancer. The nucleotide sequences at which these cross-links are formed have been defined at single nucleotide resolution in DNA fragments for several agents, including mechlorethamine, cisplatin, mitomycin C, and some structurally related agents. Taken together, the structure of duplex DNA, the sequences which are cross-linked, and the atomic sites on DNA which are linked, indicate that cross-linking occurs preferentially at locations which will result in minimal distortion of B-DNA. The proposal that this preference is primarily expressed by minimizing the energy of the transition state for conversion of monoadducts to cross-links is supported by experiments with mechlorethamine. It is suggested that extension of the modest sequence-recognizing capacity of these cross-linking agents by conjugation to highly sequence-selective “delivery vehicles” may yield second generation, targeted antitumor drugs.

A convenient method for the selective reduction of amides to amines

Abstract A variety of amides have been selectively reduced to the corresponding amines via conversion to their thioamides and treatment with triethyloxonium tetrafluoroborate followed by sodium borohydride. This procedure is compatible with isolated and conjugated double bonds, esters, intro groups, and sulfonamides.

A Convenient Method for the Conversion of Amines to Carbamates

Abstract Treatment of primary or secondary amines with bis(trimethylsilyl)acetamide followed by addition of methyl, vinyl, or 2,2,2-trichloroethyl chloroformate provides a convenient method for the preparation of the corresponding carbamates.

Preparation and diels-alder reaction of N-carbomethoxy-5-ethyl-1.2-dihydropyridine: An approach for the synthesis of catharanthine

N-carbomethoxy-5-ethyl, 1,2-dihydropyridine (1) may be prepared by the bromination of N-carbomethoxy-3-ethyl-1,2,5,6-tetrahydropyridine (10), and subsequent double dehydrobromination with EtAlCl2/HMPA; this diene undergoes Diels-Alder reaction with dimethyl methylenemalonate (2) to give the isoquinuclidine (3), an intermediate in our planned approach to catharanthine.

[3,3]-Sigmatropic rearrangement of silyl ketene acetals of methyl α-(allyloxy)acetates

Abstract Although the lithium enolate 2a undergoes [2,3]-sigmatropic rearrangement to give 4a , the silyl ketene acetals 3 undergo [3,3]-sigmatropic rearrangement to give 5 . This is the first reported [3,3]-sigmatropic rearrangement of a 1,1-dioxy-3-oxa-1,5-diene.

Intramolecular hydride transfer and cyclization of 5-oxo-Na-tosyl-14,21 -dehydrosecodine

Abstract 5-Oxo-Na-tosyl-14,21-dehydrosecodine (8) was prepared by bromination of 6 followed by double dehydrobromination with ethyl aluminum dichloride in HMPA. When a dilute solution of 8 was heated, 10 was formed via intramolecular hydride transfer and cyclization.

Claisen ortho ester rearrangement with trimethyl β-(methoxy)orthopropionate: a thermally stable synthon for the preparation of methyl α-substituted acrylates☆

Abstract Trimethyl β-(methoxy)orthopropionate, a compound which is thermally stable at 190 °C for prolonged times, may be utilized as a synthon for the preparation of methyl α-substituted acrylates via Claisen ortho ester rearrangement with allylic alcohols followed by β-elimination of methanol with base.

Synthesis of 4-Alkoxy-N-Carboalkoxy-1,2-Dihydropyridines

Abstract The synthesis of N-carboalkoxy-1,2-dihydropyridines by the method of Fowler1 is an excellent procedure for the preparation of this useful class of compounds2.

Claisen ortho ester rearrangement with trimethyl 3-(phenylseleno)orthopropionate: A synthon for the preparation of 2-substituted acrylates and α-methylene-γ-butyrolactones

Abstract Trimethyl 3-(phenylseleno)orthopropionate may be utilized as a synthon for the preparation of either 2-substituted acrylates or α-methylene-γ-butyrolactones via Claisen ortho ester rearrangement with allylic alcohols followed by oxidative-elimination of PhSeOH.

Migration of Silicon from Oxygen to Carbon in O-Trialkylsilyl Ketene Acetals

Abstract The migration of silicon from oxygen to carbon for 1 and 3 is intramolecular. The half—life of migration is not influenced by the presence of t-BuMe2SiCI or triethyIbenzylammonium chloride.