Andrew T. McPhail

X-Ray crystal structure of rocaglamide, a novel antileulemic 1H-cyclopenta[b]benzofuran from Aglaia elliptifolia

The structures and relative stereochemistries of recaglamide, a novel antileukemic 1H-cyclopenta[b]benzofuran isolated from Aglaia elliptifolia, and dehydrorocaglamide, derived from rocaglamide, have been established from spectral and single-crystal X-ray analysis.

Controlling benzylic functionality and stereochemistry: 2. Synthesis of the pseudopterosin aglycone

Homologation, cyclisation, and reduction converted the tetralin (2) to the hexahydrophenalenol (8), which was methylated to afford (19), via alkoxide-directed metalation. The degree of stereoselectivity resulting from reactions of (19) and congeners with allylsilane - Lewis acid combinations was markedly dependent upon substitution patterns, whereas Et2AlCN-SnCl4 produced pseudoaxial nitriles. The trimethyl nitrile (24) was elaborated to the pseudopterosin aglycone (4).

Synthesis and evaluation of pyrazolo[3,4-b]quinoline ribofuranosides and their derivatives as inhibitors of oncogenic Ras

Abstract A series of pyrazolo[3,4-b]quinoline ribofuranosides were prepared using the glycosylation methodology of Vorbruggen. Oxidative cleavage of the ribose moiety in 6 furnished the dialdehyde intermediate 36, which cyclizes upon reductive amination providing the morpholino compound 37. Derivatives from both the ribose and morpholino series were evaluated for their ability to inhibit the nucleotide exchange process of oncogenic Ras. 1a

Synthesis and crystal structure of the dimer bis {[bis(trimethylsilylmethyl) arsino] diphenylgallane}

Abstract The dimer [(Me 3 SiCH 2 ) 2 AsGaPh 2 ] 2 , obtained from the reaction of (Me 3 SiCH 2 ) 2 AsH with Ph 3 Ga, has been characterized by partial elemental analysis, NMR spectroscopy, cryoscopic molecular weight determination, and complete single-crystal X-ray analysis. Crystals of the dimer are triclinic, space group P 1 , with a 10.541(1), b 11.939(1), c 10.539(1) A, α 99.72(1), β 83.00(1), γ 114.55(1)°, U 1187.1 A 3 and Z = 1. The bond lenghts (GaAs 2.518(1) and GaAs′ 2.530(1) A) and bond angles (AsGaAs′ 85.08(2) and GaAsGa′ 94.92(2)°) in the centrosymmetric, and consequently planar, four-membered ring indicate a significant degree of strain.

Solution- and solid-phase synthesis of enantiomerically pure spiro oxindoles

A convenient synthesis of enantiomerically pure oxindoles using a three component reaction involving 1:3 dipolar cycloaddition reaction has been achieved using solution and solid phase chemistry.

New cembranolide analogues from the formosan soft coral Sinularia flexibilis and their cytotoxicity

Using a bioactivity-guided fractionation procedure, five cembranolides, 11-epi-sinulariolide acetate (1), 11-dehydrosinulariolide (2), sinulariolide (3), dihydrosinularin (4), and 3,4:8,11-bisepoxy-7-acetoxycembra-15(17)-en-1,12-olide (5), along with two nucleosides, 2′-deoxyadenosine and thymidine, were isolated from the Formosan soft coral Sinularia flexibilis. Moreover, 7,8-epoxy-11-epi-sinulariolide acetate (1a), 11-sinulariolide acetate (3a), dihydrosinulariolide (3b), 3,4:8,11-bisepoxy-7-hydroxycembra-15(17)-en-1,12-olide (3c), 11-acetoxyl-15(17)-dihydrosinulariolide (3d), 7,8-epoxy-11-sinulariolide acetate (3e), and 3,4:8,11-bisepoxy-7-hydroxycembra-15(17)-dihydro-1,12-olide (3f) were derived from compounds 1 and 3, respectively. These structures were deduced on the basis of physical and chemical evidence. Among them, 1a, 3d, 3e, and 3f are new cembranolide analogues. The structure of compound 1 was further confirmed by X-ray analysis. In addition, the isolated cembranolides and the analogues under went a cytotoxicity assay, and the structure-activity relationship (SAR) of these compounds was studied.

Cycloaddition of vinyl aziridines with unsaturated substrates. A novel rearrangement of an unsaturated nitro compound.

Abstract Vinylaziridine 2 undergoes reaction with electrophilic acetylenes and olefins to produce 7-membered azepine derivatives. With β-nitro-styrene however, a novel rearrangement occurs, presumably via an ene reaction to form 10 , the structure of which is definitively shown by x-ray diffraction.

A cembranolide diterpene farnesyl protein transferase inhibitor from the marine soft coral Lobophytum cristagalli

Abstract A previously described cembranolide diterpene from Lobophytum cristagalli was identified as a potent (IC50 0.15 μM) inhibitor of farnesyl protein transferase (FPT). The compound showed selectivity for FPT as compared to the closely related enzyme geranylgeranyl protein transferase-1 (IC50 5.3 μM). Kinetic evaluation suggests that this compound competes with the protein/peptide farnesyl acceptor substrate, and not with farnesyl pyrophosphate for inhibition of FPT.

STRUCTURE AND STEREOCHEMISTRY OF PSEUDOLAROLIDE-I, A NOVEL CYTOTOXIC PEROXYTRITERPENE DILACTONE FROM PSEUDOLARIX KAEMPFERI

A novel cytotoxic peroxytriterpene dilactone, pseudolarolide I, has been isolated from the seeds of Pseudolarix kaempferi, and its structure and stereochemistry have been established from spectral data in conjunction with a single-crystal X-ray analysis

Identity of coleonol with forskolin: structure revision of a base-catalysed rearrangement product

Abstract The identity of coleonol and forskolin is shown through structure revision of a rearrangement product isolated earlier from coleonol and is confirmed by direct comparison of authentic coleonol with forskolin 1 ; in addition, coleonol-B should be correctly represented by structure 4 .