Asymmetric syntheses with chiral oxazaborolidines

Wallbaum, Sabine; Martens, Jürgen

doi:10.1016/s0957-4166(00)86044-9

Cited by 385 publications

(72 citation statements)

References 77 publications

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“…Oxazaborolidines derived from chiral β-amino alcohols are regarded as important catalysts for the enantioselective reduction of C==O and C==N bonds (Corey & Helal, 1998;Deloux & Srebnik, 1993;Singh, 1992;Puigjaner et al, 1999), and for other enantioselective organic transformations (Wallbaum & Martens, 1992;Joshi et al, 1989). The 1,3,2-oxazaborolidine derived from the (S)-α,α-diphenyl prolinol, (Scheme), known as the Corey, Bakshi and Shibata (CBS) catalyst, (I), is the most efficient for the reduction of aromatic ketones (Corey et al, 1987;Mathre et al, 1991).…”

Section: Commentmentioning

confidence: 99%

A 1,3,2-oxazaborolidine dimer derived from (S)-α,α-diphenylprolinol

et al. 2004

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The reaction of (S)‐α,α‐diphenylprolinol with an excess of borane–tetrahydrofuran complex yields a stable crystalline material with the composition C34H38B2N2O2, which features a borane adduct of a spirocyclic structure with two oxazaborolidine rings joined by a central tetrahedral B atom. This dimeric oxazaborolidine complex, viz. 3,3,3′,3′‐tetraphenyl‐1,1′‐spirobi(3a,4,5,6‐tetrahydro‐3H‐pyrrolo[1,2‐c][1,3,2]oxazaborole)–7‐borane, is the dominant product under various reaction conditions; its crystal structure is consistent with 11B, 1H and 13C NMR and IR analyses.

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Section: Commentmentioning

confidence: 99%

A 1,3,2-oxazaborolidine dimer derived from (S)-α,α-diphenylprolinol

et al. 2004

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“…After oxidation of racemic alcohol 9a, ketone 16 was subjected to enantioselective reduction 13,14) by using chiral prolinol ligand (R)-17 or (S)-17, followed by reduction of a nitro group to give optically pure aniline (S)-10a and (R)-10a, respectively. Optically pure and stereochemically inversed bisamidines (R)-13j and (S)-13j were synthesized from (S) and (R)-10a by the same method as their racemate, respectively.…”

Section: Chemistrymentioning

confidence: 99%

Cinnamylindoline Derivatives: Synthesis and Factor Xa (FXa) Inhibitory Activities

Noguchi

Tanaka

Nishimata

et al. 2007

CHEMICAL & PHARMACEUTICAL BULLETIN

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In recent days, factor Xa (FXa) inhibitor attracts much attention as a promising drug candidate for anticoagulation. 3)FXa, a serine protease in the blood coagulation cascade, 4) is essential for the formation of thrombin. It plays an important role in the coagulation cascade at the convergent point of the intrinsic and the extrinsic pathway. FXa inhibitor is expected to be a novel antithrombotic with potential for the treatment and prevention of thromboembolic diseases. 5,6) In previous papers, 7,8) we reported the syntheses and FXa inhibitory activities of bisamidine compounds having indoline moiety in the center of the molecule. In these studies, we found that (R)-5-[1-(acetimidoyl)piperidin-4-yloxy]-2-(7-amidinonaphthalen-2-yl)-1-(ethanesulfonyl)indoline ((R)-1) and ({(R)-5-[1-(acetimidoyl)piperidin-4-yloxy]-2-(7-amidinonaphthalen-2-yl)indolin-1-yl}sulfonyl)acetic acid ((R)-2) exhibited potent FXa inhibitory activities (Fig. 1). However, these compounds also exhibited potent inhibitory activities against trypsin which belongs to a serine protease family. In general, compounds having selective inhibitory activity against target enzyme were favorable as drug candidates because of less possibility of unexpected adverse reaction. From this viewpoint, we searched for a potent and selective FXa inhibitor.Herein, we describe the synthesis and structure-activity relationships (SARs) and FXa selectivity of these compounds. Chemistry(E)-Substituted cinnamaldehyde intermediates 4a-e were synthesized as shown in Chart 1. 3-Cyanobenzaldehyde (3) was reacted with ylides to give corresponding substituted cinnamaldehyde 4a-c. Compound 3 and methyl acrylate (5) were coupled to give cinnamate 6d having a methoxymethyl group on the a-position. 3-Cyanoacetophenone (7) was reacted with an ylide to give cinnamate 6e having a methyl group on the b-position. Compounds 6d and 6e were converted to cinnamaldehydes 4d and 4e by 3 steps, respectively.The syntheses of bisamidine derivatives (13a-e) are outlined in Chart 2. Cinnamaldehyde 4a-e were coupled with compound 8a 7) by tetrabutylammonium fluoride (TBAF) to give the corresponding alcohols 9a-e. 9) Nitro groups of alcohols 9a-e were converted to ethanesulfonylamino groups -16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan: b Medicinal Chemistry Research Laboratories I, Daiichi Sankyo Co., Ltd.; c Biological Research Laboratories II, Daiichi Sankyo Co., Ltd.; and d Biological Research Laboratories I, Daiichi Sankyo Co., Ltd.; 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Received June 21, 2007; accepted August 10, 2007; published online August 10, 2007 A series of cinnamylindoline derivatives were synthesized, and their factor Xa (FXa) inhibitory activities and selectivity over trypsin were evaluated. Among them, some novel derivatives showed potent FXa inhibitory activities and good selectivity over trypsin. Especially, (E)-2-{5-[1-(acetimidoyl)piperidin-4-yloxy]-2-[2-(5-amidino-2-hydroxyphenyl)ethen-1-yl]indolin-1-ylsulfonyl}acetic acid (22f) having 2-hydroxy...

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“…The acetophenone 15 was therefore subjected to enantioselective reduction using freshly prepared (S)-oxazaborolidine (CBS-catalyst ) and borane-dimethyl sulphide complex, 6 to give the (αR) enantiomer 24 of the benzyl alcohol 17. 7 …”

Section: Syntheses Of the Halogenated Benzyl Alcohols 16 And 17mentioning

confidence: 99%