Gem-bisphosphonates

Sturtz, G., Preparation of acrylic or methacrylic phosphonate or gem-bisphosphonate compounds, French PatentAppl. FR 2767829, 1999 Chem. Abstr, 130, 282173, 1999. 

Guervenou, J., and Sturtz. G.. Synthesis of. gem-bisphosphonic conjugates of cortisone derivatives. Phosphorus, Sulfur Silicon Relat. Elem., 88, 1, 1994. 

In the course of synthesising enantioenriched y-keto gem-bisphosphonates having anti-arthritic and anti-inflammatory activities, Barros and Phillips have finalised organocatalytic asymmetric Michael additions of cyclic ketones to vinyl gem-bisphosphonates. The reactions were performed in the presence of (iS)-( + )-l-(2-pyrrolidininylmethyl)pyrrolidine as an organocatalyst and benzoic acid as an additive, leading to the expected Michael products in high yields, excellent diastereoselectivities (> 98% de) combined with enantioselectivities... 

Enantioselective total synthesis of ((47J,5iS)-5-Amino-4-(2,4,5-tri-fluorophenyl) cyclohex- l-enyl)-(3-(trifluoromethyl)-5,6-dihydro-[l, 2,4]tri-azolo[4,3-a]pyrazin-7(877)-yl)methanone ABT-341 (708), a DPP4 (dipeptidyl peptidase IV) inhibitor, has been completed in diphenylprolinol silyl ether (707), in the one-pot, multicomponent, reaction of nitroalkene (704), acetaldehyde (703), vinyl phosphonate (706) and amine (705) (Scheme 178) A novel, catalytic, asymmetric Michael addition of azomethine ylide (710) with p-substituted tetraethyl alkyhdene bisphosphates (709) has been realised in the presence of a chiral copper(I)/TF-Bipham-Phos (712) complex. This system provided enantioenriched unnatural i -amino acid derivatives (711) containing gem-bisphosphonates in high yields with... 

It was found that in the case of diphosphonylation reactions with cyclic aliphatic oximes, diethyl H-phosphonate is the better phosphorus reagent All bisphosphonates thus obtained show diagnostic triplets (/ === 140 Hz) at 57.8-63.6 ppm due to carbons bearing gem-diphosphonate groups in their C H] NMR spectra. 

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