M. Gary Newton

Reversal of absolute stereochemistry of the pyrrolo[2,1-b]quinazoline alkaloids vasicine, vasicinone, vasicinol and vasicinolone

Abstract The previously assigned 3 R configuration of (−)-vasicinone has been reversed and this pyrrolo[2,1-b]quinazoline-9-one has been shown to have the 3 S -configuration ( 3 ) on the basis of an X-ray diffraction study of (+)-vasicinone hydrobromide. Likewise, the 3 R stereochemistry assigned earlier to (−)-vasicine (peganine) ( 1 ) on the basis of an X-ray analysis of its hydrochloride has also been reversed by reinvestigation of the X-ray diffraction analysis of the hydrobromide. The absolute stereochemistry of the alkaloids (+)-vasicinol ( 2 ) and vasicinolone ( 5 ) which have been inter-related, should also have the 3 S -configuration. A study of the 1 H nmr spectroscopy of (−)-vasicine by the use of Moshers method using MTPA [α-methoxy-α-(trifluoromethyl)phenylacetic acid] esters indicated an exception to this model for establishing the absolute configuration.

Synthesis of enantiomerically pure cyclopropyl carbocyclic nucleosides

Abstract The enantiomeric synthesis of cyclopropyl carbocyclic nucleosides has been achieved and the key intermediate was characterized by X-ray crystallography.

Organonickel chemistry in the catalytic hydrodechlorination of polychlorobiphenyls (PCBs): ligand steric effects and molecular structure of reaction intermediates

Abstract Soluble homogeneous organophosphorus—nickel complexes have been used to detoxify polychlorinated biphenyls (PCBs) by catalyzed hydrodechlorination using NaBH 2 (OCH 2 CH 2 OCH 3 ) 2 as the hydrogen source. The reactions appear to proceed by NiL 3 oxidative addition into CCl bonds followed by hydrogenolysis of the metalcarbon bond. In model experiments with decachlorobiphenyl, the cone angle of the organophosphorus ligand L was shown to be a key factor controlling the magnitude and position of chlorine displacement. Hence, ligands leading to para displacement (e.g. ( o -MeC 6 H 4 O) 3 P), meta—para displacement (e.g. (EtO) 3 P and (PhO) 3 P), and ortho—meta—para displacement (e.g. Me 3 P and Et 3 P) were found. Significantly, the highly toxic, coplanar dioxin precursor 3,3′,4,4′-tetrachlorobiphenyl, a meta—para chlorine-substituted congener, was dechlorinated quantitatively with the Et 3 P catalyst system. Evidence for the presence of organonickel intermediates in the reaction mixtures was obtained by mass spectroscopic and X-ray diffraction studies. Of particular interest is the isolation of square planar complexes p -C 6 Cl 5 C 6 Cl 4 Ni(PEt 3 ) 2 Cl from the reaction of decachlorobiphenyl with NaBH 2 (OCH 2 CH 2 OCH 3 ) 2 —(Et 3 P) 2 NiCl 2 as the catalyst precursor and m -C 6 Cl 5 C 6 Cl 4 Ni(PEt 3 ) 2 Cl from decachlorobiphenyl—Ni(1,5-C 8 H 12 ) 2 —PEt 3 at room temperature. All are oxidative addition intermediates and precursors for decachlorobiphenyl hydrodechlorination.

1,3-Dioxolane C-Nucleosides: Asymmetric Synthesis of Four Stereoisomers of 2-[2-(Hydroxymethyl)-1,3-Dioxolan-S-yl)-1,3-Thiazole-4-Carboxamide

Abstract Asymmetric synthesis of four novel C-nucleosides, (2′R,5′R)-, (2′S,5′R)-, (2′S,5′S)- and (2′R,5′S)-2-[2-hydroxymelhy])-1,3-dioxolan-5-yl]-1 ,3-thiazole-4-carboxamide has been accomplished by the condensation of key intermediates, 2-(1R- and 1S-glycol-1-yl)-4-ethoxycarbonyl-1,3-thiazole with 2-benzoyloxy acetaldehyde dimethyl acetal.

ASYMMETRIC SYNTHESIS OF (2'R, 4'R) AND (2'S, 4'S)-1,3-DIOXOLANYL TRIAZOLE C-NUCLEOSIDES

Abstract In view of biological activities of both 1,3-dioxolanyl nucleosides and C-nucleosides, d - and l -1,3-dioxolanyl C-nucleosides have been synthesized as potential antiviral and/or anticancer agents. Asymmetric synthesis of four new optically pure d - and l -1,3-dioxolanyl triazole C-nucleosides has been accomplished via key intermediate 5a and 5b starting from d - and l -2,3-O-isopropylidene glyceraldehyde. The stereochemical assignments of synthesized compounds were unambiguously made based on NMR studies as well as X-ray crystallographic studies. The synthesized nucleosides have been evaluated against HIV and hepatitis B virus, however, no significant antiviral activity was observed.

Crytocaryone: A revised structure

Cryptocaryone, formulated earlier as the chalcone 1, has been shown to have structure 2 by an X-ray crystallographic analysis. Carbon-13 assignments are given.

On increasing protein-crystallization throughput for X-ray diffraction studies.

Two recent developments, a novel screening/optimization strategy that considerably reduces the number of trials required to produce diffraction-size crystals and a simple modification that doubles the screening capacity of the Douglas Instruments ORYX 1-6 protein-crystallization robot, have been implemented into a structural genomics project. The new two-step screening/optimization strategy yields diffraction-quality crystals directly from the screening process, reducing the need for further optimization. The ORYX modification involves the addition of extensions to the sample- and oil-delivery arms and software modifications that allow two plates to be set up simultaneously.

The structure of the π-molecular complex between 1,4-dihydro-9,10-anthrahydroquinone and 1,4-dihydro-9,10-anthraquinone

The structure of the π-molecular complex (10) was assigned on the basis of the solid state13C-nmr spectrum. The solid state13C-nmr spectrum of quinhydrone (12) has also been determined. Accurate1H and13C chemical shift assignments have been made for the compounds3,5,6,7,8, and10 on the basis of HMQC and HMBC spectral data. The π-molecular complex10 crystallizes in the space groupP21In with cell parameters:a=4.052 (1) Å,b=6.477 (1) Å,c=19.093 (2) Å, β=90.17 (1)o,z=1,Dc=1.400 g mc−32. Crystal and molecular structure of the title compound, C28H22O4, has been determined by an X-ray analysis of10 by direct methods from diffractometer data and refined by full-matrix least-squares

Revised structures of pratorinine and pratorimine

Abstract Two phenanthridone alkaloids isolated from the bulbs of Crinum bulbispermum L. have been shown to be identical with pratorinine and pratorimine. The structure proposed earlier for pratorinine has been revised to 3 on the basis of an X-ray structure analysis and the structure of pratorimine has been shown to be 2.

Heterolytic fragmentation of deltaline, a norditerpenoid alkaloid

Abstract The rearrangement product obtained by treatment of the norditerpenoid alkaloid deltaline ( 1 ) with SOCl 2 in moist benzene has been assigned structure 5 . This compound was also obtained by treatment of 10-chloro-10-deoxydeltaline ( 4 ) with aqueous MeOH. However, when ( 4 ) was treated with methanolic KOH, a novel rearranged pyrrolidine ( 8 ) was obtained. Structures 5 and 8 for these heterolytic fragmentation products were established by nmr spectroscopic data and an X-ray crystal structure determination of 8 .