C2-Symmetric Chiral Pentacyclic Guanidine: A Phase-Transfer Catalyst for the Asymmetric Alkylation of tert-Butyl Glycinate Schiff Base

Kita, Tetsuya; Georgieva, Angelina; Hashimoto, Yuichi; Nakata, Tadashi; Nagasawa, Kazuo

doi:10.1002/1521-3773(20020802)41:15<2832::aid-anie2832>3.0.co;2-q

Cited by 180 publications

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“…[24][25][26][27] or other designed catalysts (for representative examples, see refs. [28][29][30][31][32], only a few synthetic applications for complex natural products have been reported (23). Recently, we developed two-center catalysts that promote phase-transfer alkylations and Michael reactions with high substrate generality (14).…”

Section: Resultsmentioning

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.

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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...

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Section: Resultsmentioning

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.

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“…Our results and the selectivities observed are in agreement with the reactions reported by Nagasawa using structurally similar pentacyclic guanidine catalysts. 8 We next focused on the application of 7a to the PTC epoxidation of chalcones 10a-e 9 (Scheme 3) and found it to be an excellent catalyst for this transformation. We initially investigated the epoxidation of chalcone 10a (R 1 = R 2 = Ph) with NaOCl and found that the catalyst was effective over a range of 0.1 to 0.025 equivalents and gave the chalcone epoxide 11a in consistent ee and in high yields ( Table 2, entries 1-3).…”

Section: Phase Transfer Alkylation and Epoxidation Reactionsmentioning

confidence: 99%

Synthesis, applications and mechanistic investigations of C2 symmetric guanidinium salts

et al. 2016

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Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractThe Guanidinium catalysts 7a-e were prepared and applied to the phase transfer alkylation of glycinate Schiff's base 8 in 21-86% ee in addition to the phase transfer epoxidation of the chalcones 10a-e in 85-94% ee. The pK a values of 7a-d were determined to be in the range 13.2-13.9, which supports a standard phase transfer mechanism for these processes. The use of 7a and 7e as catalysts for the addition of nucleophiles in Michael addition reactions was investigated and both were found to be effective catalysts. A counterion effect was apparent in these reactions, however no enantiomeric enrichment of the adducts was observed.

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“…8) Nagasawa and co-workers reported chiral guanidinium salts as a new type of PTC that promoted O'Donnell's alkylation under PTC conditions. 9) In this communication, we report the catalytic asymmetric Michael reaction of a glycine Schiff base using bis-ammonium salts as PTCs. [10][11][12][13][14][15][16] Binaphthol and its derivatives are known to be a versatile starting compound for the preparation of chiral catalyst.…”

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confidence: 99%

Asymmetric Michael Reaction Promoted by New Chiral Phase-Transfer Catalysts

Arai

Tokumaru

Aoyama

2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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A catalytic asymmetric Michael reaction promoted by new chiral quaternary ammonium salts is described. The products are obtained with moderate ee (up to 75% ee), and the enantioselectivity is strongly dependent on both the substituents on the aromatic rings and the ammonium moiety in the catalysts.Key word asymmetric synthesis; chiral ammonium salt; phase-transfer catalysis; Michael reaction Phase-transfer catalysts (PTCs) offer many advantages as organic reagents for the transformation of organic molecules, including mild reaction conditions (water can be used as a solvent), simple reactions, environmental benign and low cost, and they have recently been considered to be a useful tool in the development of green chemistry. In particular, onium salts have been recognized as one of the most powerful PTCs due to their facile preparation and structural diversity, and their utility in asymmetric synthesis has been investigated. The first successful examples of asymmetric catalysis with a chiral ammonium salt as a PTC were reported independently by Dolling 2) and O'Donnell 3) in the mid-to late 1980's. The catalysts they have reported for use in enantioselective alkylation are both cinchona alkaloid derivatives. These two pioneering examples in asymmetric PTC chemistry have been applied to other asymmetric reactions. [4][5][6] On the other hand, Maruoka and co-workers reported excellent results in the asymmetric alkylation of glycine Schiff base using designer ammonium salts. 7) Belokon and Kagan also achieved high enantioselectivities using nickel complexes as PTCs.8) Nagasawa and co-workers reported chiral guanidinium salts as a new type of PTC that promoted O'Donnell's alkylation under PTC conditions. 9) In this communication, we report the catalytic asymmetric Michael reaction of a glycine Schiff base using bis-ammonium salts as PTCs. [10][11][12][13][14][15][16] Binaphthol and its derivatives are known to be a versatile starting compound for the preparation of chiral catalyst. And also the functionalization of 2, 3 and 6 positions could provide a various analogues for each asymmetric transformation. Moreover, bis-ammonium salts would be expected to accelerate the reaction due to the two reaction site and it would prevent the undesired reaction pathway which chiral PTCs do not concern. Based upon these, we started to investigate the preparation of symmetrical bis-ammonium salts and survey the asymmetric Michael reaction. First of all, we begun to prepare the 2,3-disubstituted binaphthyl and transformed to bis ammonium salt, as outlined in Chart 1. Di-MOM ether of (S)-BINOL 1 was formylated at the 3,3Ј-position and subsequent deprotection of MOM groups by treatment with acid gave 2 in 65% yield. Benzylation of the phenolic function of 2 with 4-trifluoromethylbenzyl bromide, reduction of the formyl groups and subsequent halogenation of the resulting primary diol with CBr 4 -PPh 3 gave the corresponding bis(bromomethyl)binaphthyl 5 in 68% overall yield. Quaternarization of 5 with triethylamine under reflux condition...

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C2-Symmetric Chiral Pentacyclic Guanidine: A Phase-Transfer Catalyst for the Asymmetric Alkylation of tert-Butyl Glycinate Schiff Base

Abstract: The enantioselective alkylation of the Schiff base 2 was carried out in the presence of a novel phase‐transfer catalyst, the guanidine‐containing pentacyclic compound 1. The product 3 was obtained with enantiomeric excesses of 76–90 % (see scheme).

Cited by 180 publications

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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

Synthesis, applications and mechanistic investigations of C2 symmetric guanidinium salts

Asymmetric Michael Reaction Promoted by New Chiral Phase-Transfer Catalysts

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