Catalytic Asymmetric Epoxidation of Enones Using La−BINOL−Triphenylarsine Oxide Complex:  Structural Determination of the Asymmetric Catalyst

Nemoto, Tetsuhiro; Ohshima, Takashi; Yamaguchi, Kentaro; Shibasaki, Masakatsu

doi:10.1021/ja004201e

Cited by 167 publications

(74 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To address this issue, we applied asymmetric phase-transfer catalysis (PTC) promoted by two-center catalysts, which were recently developed by our group (14), to the syntheses of 1a as well as its analogs. Here, we report the enantioselective syntheses of aeruginosin 298-A and its analogs (15) by using asymmetric PTC and the catalytic asymmetric epoxidation of an ␣,␤-unsaturated imidazolide, which was also recently developed by our group (16)(17)(18)(19)(20)(21)(22). Moreover, serine protease inhibitory activities of 1a and its analogs were examined, leading to the future discovery of analogs possessing higher and more selective protease inhibitor potencies than those of the natural products.…”

mentioning

confidence: 99%

Enantioselective syntheses and biological studies of aeruginosin 298-A and its analogs: Application of catalytic asymmetric phase-transfer reaction

Fukuta

Ohshima

Gnanadesikan

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Aeruginosin 298-A was isolated from the freshwater cyanobacterium Microcystis aeruginosa (NIES-298) and is an equipotent thrombin and trypsin inhibitor. A variety of analogs were synthesized to gain insight into the structure-activity relations. We developed a versatile synthetic process for aeruginosin 298-A as well as several attractive analogs, in which all stereocenters were controlled by catalytic asymmetric phase-transfer reaction promoted by twocenter asymmetric catalysts and catalytic asymmetric epoxidation promoted by a lanthanide-BINOL complex. Furthermore, serine protease inhibitory activities of aeruginosin 298-A and its analogs were examined. P roteolytic reactions control many important biologic processes; thus, the discovery of new selective proteolysis inhibitors continues to receive significant attention (1). Several serine proteases have been selected as potential therapeutic targets, such as the coagulation enzyme factors Xa, VIIa, and IIa (thrombin) (2) and urokinase-type plasminogen activator (3-5). The catalytic sites of the different serine proteases involved have a highly homologous region (2); therefore, engineering high selectivity would be especially challenging. Cyanobacteria produce several unique biologically active peptides, such as microcystins, microviridin, nodularin, and puwainaphycins. Aeruginosin 298-A (1a) was isolated by Murakami and coworkers from the freshwater cyanobacterium Microcystis aeruginosa (NIES-298) (6) and is an equipotent thrombin and trypsin inhibitor (7) (Fig. 1). Since 1994, Ͼ10 aeruginosins have been isolated by Murakami (6-9), along with microcin SF608, which was isolated by Carmelli and coworker (10). These compounds have a tetrapeptide-like structure including nonstandard ␣-amino acids such as 3-(4-hydroxyphenyl)lactic acid (Hpla) and 2-carboxy-6-hydroxyoctahydroindole (Choi). Of the aeruginosin family, aeruginosin 102-A (1b) is reported to have the highest activity (7,8). More potent analogs in terms of selectivity and activity, however, need to be developed. Although the total synthesis of 1a was reported by Bonjoch et al. (11,12) and Wipf and Methot (13), the development of a highly versatile synthetic method is required to gain insight into the structure-activity relations by the syntheses of a variety of analogs. To address this issue, we applied asymmetric phase-transfer catalysis (PTC) promoted by two-center catalysts, which were recently developed by our group (14), to the syntheses of 1a as well as its analogs. Here, we report the enantioselective syntheses of aeruginosin 298-A and its analogs (15) by using asymmetric PTC and the catalytic asymmetric epoxidation of an ␣,␤-unsaturated imidazolide, which was also recently developed by our group (16)(17)(18)(19)(20)(21)(22). Moreover, serine protease inhibitory activities of 1a and its analogs were examined, leading to the future discovery of analogs possessing higher and more selective protease inhibitor potencies than those of the natural products. The knowledge gained provides important inform...

show abstract

mentioning

confidence: 99%

Enantioselective syntheses and biological studies of aeruginosin 298-A and its analogs: Application of catalytic asymmetric phase-transfer reaction

Fukuta

Ohshima

Gnanadesikan

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…102,104) The new asymmetric catalyst system consisting of La(O-iPr) 3 , BINOL, and Ph 3 AsϭO in a ratio of 1 : 1 : 1 [La-BINOL-Ph 3 AsϭO (1 : 1 : 1) complex 64] had a broad generality for enones, affording the products in excellent yield and up to greater than 99% ee, even at room temperature. 103) Almost all reactions proceeded to completion in reasonable reaction times using 5 mol% of the catalyst 64 (Table 5). Epoxidation of both aryl (entries 1-4) and alkyl (entries 5-9) ketone-type substrates proceeded smoothly and afforded the corresponding epoxy ketones in excellent yield (up to 99% yield) and enantiomeric excess (up to Ͼ99% ee).…”

Section: Catalytic Asymmetric Epoxidation 3-1 Catalytic Asymmetric Ementioning

confidence: 96%

“…25) Compared with the previous synthesis using the Michael adduct of malonate as a starting material (3AE47), the present synthesis requires fewer steps (5 steps vs. 9 steps) and all the carbon atoms of the Michael donor were efficiently utilized for the construction of the carbon skeleton of 47 without C-C bond cleavage. [102][103][104] Protein kinase C (PKC) is thought to have a principal role in cellular signal transduction and is a target of anticancer drug screening. 105,106) (ϩ)-Decursin (51) (Fig.…”

Section: )mentioning

confidence: 99%

“…The unique feature of the catalyst is believed to be a result of a synergistic cooperation of metals and ligands. [4][5][6][7][8] Although the original catalyst [La-BINOL (1 : 1)] had low to moderate reactivity and selectivity (28% yield, 20% ee for La-BINOL and 88% yield, 83% ee for Yb-BINOL) (Table 4, entries 3, 4), [125][126][127] after optimization of the reaction conditions, the La-BINOL complex with triphenylphosphine oxide (Ph 3 PϭO) 129,130) or triphenylarsine oxide (Ph 3 AsϭO) [102][103][104] was highly effective for catalytic asymmetric epoxidation. 131) In terms of atom economy, the best result was obtained using 1 eq of Ph 3 AsϭO to La(O-i-Pr) 3 78) -BINOL (94%, 96% ee, entry 12).…”

Section: Catalytic Asymmetric Epoxidation 3-1 Catalytic Asymmetric Ementioning

confidence: 99%

“…6), laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF-MS), kinetic studies, and asymmetric amplification studies. 103,104) The proposed mechanism of the epoxidation is shown in Fig. 7.…”

Section: Catalytic Asymmetric Epoxidation 3-1 Catalytic Asymmetric Ementioning

confidence: 99%

See 2 more Smart Citations

Enantioselective Total Syntheses of Several Bioactive Natural Products Based on the Development of Practical Asymmetric Catalysis

Ohshima

2004

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

I present herewith enantioselective total syntheses of several bioactive natural products, such as (؊)-strychnine, (؉)-decursin, (؊)-cryptocaryolone diacetate, (؊)-fluoxetine, and aeruginosin 298-A, based on practical asymmetric catalyses (Michael reaction, epoxidation, and phase-transfer reaction) that I developed with coworkers in Prof. Shibasaki's group over the past 5 years. In the first part of this review, I discuss the great improvement of catalyst efficiency in an ALB-catalyzed asymmetric Michael reaction of malonate and application to the pre-manufacturing scale (greater than kilogram scale) and enantioselective total synthesis of (؊)-strychnine with the development of novel domino cyclization. To broaden the substrate generality of the Michael reaction, we developed a highly stable, storable, and reusable La-O-linked-BINOL complex. Further extension of the reaction using b b-keto ester as a Michael donor was achieved with the development of a La-NR-linked-BINOL complex, thereby improving indole alkaloid syntheses. In the second section, I discuss enantioselective total synthesis of (؉)-decursin using catalytic asymmetric epoxidation. To achieve the synthesis, we developed a new La-BINOL-Ph 3 As‫؍‬O (1 : 1 : 1) complex catalyst system, which has much higher reactivity and broader substrate generality than the previously developed catalyst systems. This allowed us to achieve catalytic asymmetric epoxidation of a a,b b-unsaturated carboxylic acid derivatives with high enantioselectivity and broad substrate generality for the first time by changing the lanthanide metal and reaction conditions. Among them, catalytic asymmetric epoxidation of a a,b b-unsaturated morpholinyl amides is quite useful in terms of synthetic utility of the corresponding a a,b b-epoxy morpholinyl amides. Highly catalyst-controlled enantio-or diastereoselective epoxidation of the a a,b b-unsaturated morpholinyl amides, coupled with diastereoselective reduction of b b-hydroxy ketones, enabled the synthesis of all possible stereoisomers of 1,3-polyol arrays with successful enantioselective total synthesis of several 1,3-polyol natural products, such as (؊)-cryptocaryolone diacetate. In addition, the development of a new regioselective epoxide-opening reaction of a a,b b-epoxy amides to the corresponding a a-and b b-hydroxy amides enhanced the usefulness of the present epoxidation and was applied to the enantioselective total synthesis of (؊)-fluoxetine. In the final section, I report the development of a new asymmetric two-center organocatalyst (TaDiAS) and its application to the enantioselective synthesis of aeruginosin 298-A and its analogues. Because of the remarkable structural diversity of TaDiAS, a practical asymmetric phase-transfer reaction with broad substrate generality was achieved. As a result, we succeeded in developing a highly versatile synthetic method for aeruginosin 298-A and its analogues. Inhibitory activity studies of the compounds against the serine protease trypsin provided preliminary information about their str...

show abstract

(R)-1,1′-Bi-2,2′-naphthol

Mikami

Motoyama

Brunel

2005

Encyclopedia of Reagents for Organic Synthesis

View full text Add to dashboard Cite

Catalytic Asymmetric Epoxidation of Enones Using La−BINOL−Triphenylarsine Oxide Complex: Structural Determination of the Asymmetric Catalyst

Cited by 167 publications

References 26 publications

Enantioselective syntheses and biological studies of aeruginosin 298-A and its analogs: Application of catalytic asymmetric phase-transfer reaction

Enantioselective syntheses and biological studies of aeruginosin 298-A and its analogs: Application of catalytic asymmetric phase-transfer reaction

Enantioselective Total Syntheses of Several Bioactive Natural Products Based on the Development of Practical Asymmetric Catalysis

(R)-1,1′-Bi-2,2′-naphthol

Contact Info

Product

Resources

About