01950nas a2200253   4500008004100000022001400041245009600055210006900151260000900220490000700229520108400236653004101320653002501361653001501386653003001401100002501431700002201456700002101478700001901499700001701518700002401535700002201559856011501581       2025                        eng d  a1861-472800aStudies on the stereoselective synthesis of sacubitril via a chiral amine transfer approach0 aStudies on the stereoselective synthesis of sacubitril via a chi  cMAR 0 v203 a<p>
	We present a comprehensive account of our efforts directed towards the synthesis of sacubitril, a neprilysin inhibitor used in combination with valsartan and marketed as Entresto (TM). Our initial approach to the formal synthesis of sacubitril employed a chiral pool strategy, utilizing (S)-pyroglutamic acid as a key building block and Cu(I)-mediated Csp2-Csp3 cross-coupling as a key transformation. Further investigations led to the development of chiral amine transfer (CAT) reagents-based stereoselective synthesis. This involved the E-selective construction of gamma-ylidene-butenolide from readily available biphenyl bromide and 4-pentynoic acid, the conversion of this butenolide to its ene-lactam using chiral amine, and substrate-controlled diastereoselective reduction of ene-lactam using Et3SiH or Pd/C, H2 (overall chiral amine transfer) as key transformations. Antipodal lactam intermediates were synthesized using corresponding chiral amines, and the stereochemical outcomes during the ene-lactam reduction with Et3SiH were rationalized by DFT studies.</p>
10aChiral Amine Transfer (CAT) approach10aChiral pool approach10aSacubitril10astereoselective synthesis1 aSadanande, Megha, V.1 aThorat, Sagar, S.1 aSharma, Himanshu1 aSingh, Geetika1 aVanka, Kumar1 aGonnade, Rajesh, G.1 aKontham, Ravindar  uhttps://library.ncl.res.in/content/studies-stereoselective-synthesis-sacubitril-chiral-amine-transfer-approach01455nas a2200181   4500008004100000022001400041245013700055210006900192260000800261300001400269490000700283520076600290100002501056700002001081700002401101700002201125856012601147       2026                        eng d  a0022-326300aDivergent synthesis of meyers' lactams and medium lactams via cyclocondensation of γ-ylidene-butanolides with chiral amino alcohols0 aDivergent synthesis of meyers lactams and medium lactams via cyc  cAPR  a5138-51580 v913 a<p>
	A novel methodology for constructing Meyers' lactams (pyrrolidino-oxazolidines), related to biologically potent natural and synthetic scaffolds, has been developed via an unprecedented tandem cyclocondensation of chiral 2-amino alcohols and gamma-ylidene-butanolides. The process proceeds through the initial formation of an ene-lactam intermediate, followed by a Bro/nsted acid (PPTS)-catalyzed ring closure. Under stoichiometric amounts of a Lewis acid (TiCl4), the same set of building blocks affords medium lactams featuring eight-membered ring systems with an exo-enol ether segment. This divergent synthetic strategy enables the efficient generation of a library of Meyers' lactams and medium lactams with good yields and diastereoselectivity.</p>
1 aSadanande, Megha, V.1 aSharma, Paridhi1 aGonnade, Rajesh, G.1 aKontham, Ravindar  uhttps://library.ncl.res.in/content/divergent-synthesis-meyers-lactams-and-medium-lactams-cyclocondensation-%CE%B3-ylidene