Application of New Efficient Hoveyda–Grubbs Catalysts Comprising an N→Ru Coordinate Bond in a Six-Membered Ring for the Synthesis of Natural Product-Like Cyclopenta[b]furo[2,3-c]pyrroles

The ring rearrangement metathesis (RRM) of a trans-cis diastereomer mixture of methyl 3-allyl-3a,6-epoxyisoindole-7-carboxylates derived from cheap, accessible and renewable furan-based precursors in the presence of a new class of Hoveyda–Grubbs-type catalysts, comprising an N→Ru coordinate bond in a six-membered ring, results in the difficult-to-obtain natural product-like cyclopenta[b]furo[2,3-c]pyrroles. In this process, only one diastereomer with a trans-arrangement of the 3-allyl fragment relative to the 3a,6-epoxy bridge enters into the rearrangement, while the cis-isomers polymerize almost completely under the same conditions. The tested catalysts are active in the temperature range from 60 to 120 °C at a concentration of 0.5 mol % and provide better yields of the target tricycles compared to the most popular commercially available second-generation Hoveyda–Grubbs catalyst. The diastereoselectivity of the intramolecular Diels–Alder reaction furan (IMDAF) reaction between starting 1-(furan-2-yl)but-3-en-1-amines and maleic anhydride, leading to 3a,6-epoxyisoindole-7-carboxylates, was studied as well.

Optically Active Transition Metal Compounds, 136 [1]. An Octahedral Molybdenum Complex (P-P’)Mo(CO)4 with a Chiral Secondary Phosphorus Atom

Reaction of (η6-C6H5CH3)Mo(CO)3 with the easily accessible chiral chelate ligand P,P,Pʹ-tris- [(+)-9-phenyldeltacyclan-8-yl]-1,2-bis(phosphanyl)benzene P-P’ afforded the octahedral molybdenum carbonyl derivate (P-P’)Mo(CO)4 1 as a diastereomer mixture 1a (74%) and 1b (26%). Crystallization gave single crystals of (SP)-(P-P’)Mo(CO)4 1a. The X-ray structure analysis of compound 1a revealed the formation of an unusual triple-decker π-stack in the solid state.

Synthesis and In Vitro Biological Evaluation of β,γ-Methano Analogues of Methotrexate and Aminopterin

Summaryβ,γ-Methano derivatives of methotrexate (MTX) and aminopterin (AMT) were synthesized with the aim of assessing the effect of this side-chain modification on dihydrofolate reductase (OHFR) inhibition, folylpolyglutamate synthetase (FPGS) inhibition, and tumor cell growth inhibition. Mixed carboxylic-carbonic anhydride (MCA) coupling of 4-amino-4-deoxy-N10-methylpteroic acid (mAPA) and dimethyl trans-α-(2-carboxycyclopropyl) glycinate, followed by alkaline hydrolysis, afforded N-( 4-amino-4-deoxy-N10-methylpteroyl)-α-( trans-2-carboxycyclopropyl)glycine (β,γ-methanoMTX) as a mixture of the four possible diastereomers with trans substitution on the cyclopropane ring. N-(4-Amino-4-deoxypteroyl)-trans-α.-(2-carboxycyclopropyl) glycine (β,γ-methanoAMT) , also as a diastereomer mixture, was obtained from 4-amino-4-deoxy-N10 - formylpteroic acid (fAPA) and dimethyl trans-α-(2-carboxycyclopropyl)-glycinate by MCA coupling and alkaline hydrolysis of the ester and N10-formyl groups. β,γ-MethanoMTX and β,γ-methanoAMT may be viewed as MTX and AMT analogues with a conformationally restricted side chain. In vitro biological activity data for these novel compounds support the view that the active site of DHFR, already known for its ability to tolerate modification of the γ-carboxyl group of MTX and AMT, can likewise accommodate substitution on the β- and γ-carbons.