Asymmetric Synthesis and Application of Î±-Amino Acids - American

Chapter 19

Preparation of Chiral Amino Acid Intermediates for Synthesis of Pharmaceutical Compounds Using

Downloaded by EAST CAROLINA UNIV on September 18, 2015 | http://pubs.acs.org Publication Date: June 14, 2009 | doi: 10.1021/bk-2009-1009.ch019

Amino Acid Dehydrogenases Ronald L. Hanson Process Research and Development, Bristol-Myers Squibb, One Squibb Drive, New Brunswick, NJ 08903

Amino acid dehydrogenases are useful for preparation of L- or D-α-amino acids from the corresponding α-keto acids. The reactions require NH , NAD(P)H and a second enzyme, usually formate or glucose dehydrogenase, for regeneration of the NAD(P)H. The enzymes are effective at high substrate concentrations and have very high enantioselectivity. Examples of the use of amino acid dehydrogenases for the preparation of some chiral intermediates used for the synthesis of drug candidate compounds are described. 3

Introduction α-Amino acids are useful intermediates for preparation of many pharmacologically active compounds. Several enzymatic approaches have been applied for the preparation of both D and L-amino acids including hydantoinases combined with carbamoylases or HN0 , (1-4) N-acylases, (1,5) amidases, (6,7) hydrolysis of esters with esterase or proteases, (8-10) transaminases, (11,12) and amino acid dehydrogenases. Of these approaches, we have found the reductive amination of ct-keto acids using amino acid dehydrogenases to be one of the most useful methods because the enzymes have good stability, broad substrate specificity and very high enantioselectivity, are effective at high substrate concentrations, and the reactions have favorable equilibria which are further enhanced when the reductive aminations are coupled to a suitable enzymatic cofactor regeneration system. Recent excellent reviews on the amino acid dehydrogenases cover the sources, substrate specificities and other 2

306

© 2009 American Chemical Society

In Asymmetric Synthesis and Application of -Amino Acids; Soloshonok, V., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2009.

307 properties of available enzymes, enzyme structures and reaction mechanisms, and some examples of their synthetic utilities (13,14). An example of a reductive amination reaction is shown in figure 4.


Performing reductive amination reactions requires first screening a collection of

amino acid dehydrogenases against the intended keto acid substrate to find the most effective enzyme. Commercially available enzymes may be screened or a suitable enzyme may be found by screening cell extracts from likely source strains in a culture collection. In cases where the gene sequence for the amino acid dehydrogenase has been reported, the gene can be cloned from the source organism using PCR, and the enzyme expressed in E. coli or other host. A second enzyme is needed for regeneration of the pyridine nucleotide cofactor. For most enzymes, the required cofactor is NADH but NADPH is required in some cases. Yeast formate dehydrogenase is commonly used for NADH regeneration, (15-17) and glucose dehydrogenase usuallyfromBacillus species may be used for either NADH or NADPH regeneration (18,19). Mutated formate dehydrogenases from Pseudomonas (20) and Saccharomyces cerevisiae (21) capable of NADPH regeneration have also been described. Formate dehydrogenase has the advantage that the product CO2 is easy to remove from the reaction. Glucose dehydrogenase has the advantages of working with either NAD or NADP and having a much higher specific activity than formate dehydrogenase. Amino acid dehydrogenase reactions have E° of -0.13 to -0.14 V (22). Using the glucose dehydrogenase (E° of -0.45) (22) or formate dehydrogenase reactions (E° of -0.42V) (22) to regenerate NADH provides a large Δ Ε to drive the reaction to completion. Phosphite dehydrogenase has also been recently introduced for regeneration of NADH (23) and a genetically evolved version for regeneration of NADPH has also been reported (24). Glucose, formate and phosphite dehydrogenases are all commercially available. When the enzymes are prepared by fermentation rather than obtained from a commercial supplier, it may be advantageous to clone and express both the amino acid dehydrogenase and cofactor regeneration enzymes in the same host. Reaction conditions are chosen that are compatible with both enzymes and also with the stability of the keto acid substrate. Because the reactions go nearly to completion, the product is readily isolated either by direct crystallization or by adsorption at low pH on a Dowex-50 H resin, washing with water, then elution with NH OH solution. Some examples of the use of amino acid dehydrogenases to prepare chiral intermediates for synthesis of drug candidate compounds are given below. 0

+

4

L-P-Hydroxyvaline L-P-hydroxyvaline (1), an intermediate used for synthesis of the monobactam antibiotic drug candidate tigemonam (Figure 1), was initially prepared from racemic β-hydroxyvaline by a classical chemical resolution


308 method. A commercially available (although expensive) leucine dehydrogenase from Bacillus species was then found to carry out the reductive amination of ctketo-P-hydroxyisovalerate to give L-P-hydroxyvaline (25). Bacillus strains from our culture collection were screened to find an alternative source of a suitable enzyme. Reductive amination activity for ct-keto-P-hydroxyisovalerate was found in most of the Bacillus strains screened (including B. megaterium, B. subtiis, B. cereus, B. pumilus, B. licheniformis B. thuringiensis, B. brevis) with the highest specific activity found in B. sphaericus ATCC 4525. Either formate dehydrogenase from Candida boidinii or glucose dehydrogenase from Bacillus megaterium was used for regeneration of NADH. pH 8.5 was optimal for both glucose dehydrogenase from Bacillus megaterium and leucine dehydrogenase from Bacillus sphaericus. For the enzyme from B. sphaericus ATCC 4525, the apparent Km for ct-keto-P-hydroxyisovalerate was 11.5 mM (sufficiently low considering that the reaction was run at 0.25 to 0.5 M of the keto acid) and the apparent V for ct-keto-P-hydroxyisovalerate was 41% of the value for otketoisovalerate (reported to be the best substrate for reductive amination by leucine dehydrogenase), making leucine dehydrogenase from B. sphaericus ATCC 4525 very suitable for synthesis of this intermediate.


f

m a x

L-6-Hydroxynorleucine The initial synthesis of Vanlev (Figure 2), a vasopeptidase inhibitor intended for the treatment of hypertension required L-6-hydroxynorleucine (2) as an intermediate (26). In the initial route, racemic N-acetyl-6hydroxynorleucine was treated with L-acylase from hog kidney to prepare the required amino acid. Because the resolution with acylase gave a theoretical maximum yield of only 50% and required separation of the desired product from the unreacted enantiomer at the end of the reaction, we subsequently tried to prepare the amino acid by reductive amination of the corresponding ketoacid (27) 2-Keto-6-hydroxyhexanoic acid (in equilibrium with its cyclic hemiketal form) was prepared by chemical synthesis starting from 4-chloro-l-butanol, which was O-protected, then converted to a Grignard reagent which was added to diethyl oxalate, followed by hydrolysis of the ester and deprotection of the hydroxyl group. Initial screening, with formate dehydrogenase for regeneration of NADH, showed that phenylalanine dehydrogenase from Sporosarcina sp. and beef liver glutamate dehydrogenase converted 2-keto-6-hydroxyhexanoic acid completely to L-6-hydroxynorleucine. Leucine dehydrogenase partially purified from Bacillus sphaericus ATCC 4525 and alanine dehydrogenase from Bacillus subtilis were not active. Additional screening with spectrophotometric enzyme assays (i.e., monitoring the rate of NADH oxidation in the reaction) of commercially available amino acid dehydrogenases and extracts of 132 cultures



309

+

C0 - [(CH3) N CH CH OH] tigemonam 2

3

2

2

2

Figure 1. Structures of L-P-hydroxyv aline and tigemonam

Figure 2. Structures of L-6-hydroxynorleucine 2, L-allysine ethylene acetal 4, and Vanlev (omapatrilat, BMS186716)



310 from our collection identified several other active enzymes, with extract from Thermoactinomyces intermedins ATCC 33205 found to contain the most active enzyme. This strain has been reported to be a source of thermostable phenylalanine dehydrogenase (28) as well as leucine dehydrogenase (29). Beef liver glutamate dehydrogenase was used for preparative reactions at 10% total substrate concentration. NADH was regenerated using glucose dehydrogenase from Bacillus megaterium. The optimum pH for glutamate dehydrogenase with this substrate was determined to be about 8.8, and glucose dehydrogenase as stated above has a broad pH optimum centered at about 8.5. The reaction, carried out at pH 8.75, was complete in about 3 h with a reaction yield of 89% and ee >99%. The product of the glucose dehydrogenase reaction is gluconolactone which is hydrolyzed to gluconic acid. NH OH was added from a pH stat to maintain pH 8.75 during the reaction and was used to follow the time course of the reaction. Chemical synthesis and isolation of 2-keto-6-hydroxyhexanoic acid required several steps. In a second more convenient process (Figure 3), the ketoacid was prepared by treatment of racemic 6-hydroxynorleucine (produced by hydrolysis of commercially available 5-(4-hydroxybutyl) hydantoin) with Damino acid oxidase and catalase. After the ee of the remaining L-6hydroxynorleucine had risen to >99%, the reductive amination procedure was used to convert the mixture containing 2-keto-6-hydroxyhexanoic acid and L-6hydroxynorleucine entirely to L-6-hydroxynorleucine with yields of 91 to 97% and ee >99%. Sigma porcine kidney D-amino acid oxidase and beef liver catalase or Trigonopsis variabilis whole cells (source of oxidase and catalase) (30) were used successfully for this transformation. 4

L-AHysine Ethylene Acetal In the original route to Vanlev, L-6-hydroxynorleucine was coupled with Sacetyl-N-Cbz-L-homocysteine, then oxidized to the aldehyde (26). In the final route, a process for the production of L-allysine ethylene acetal (4) by enzymatic reductive amination of the corresponding keto acid 3 was developed and scaled up to avoid this oxidation step (Figure 4 ) (31). Screening of commercially available amino acid dehydrogenases as well as some strains from our culture collection showed that glutamate, alanine, leucine and phenylalanine dehydrogenases (listed in order of increasing effectiveness) gave some of the desired product. An extract of Thermoactinomyces intermedius ATCC 33205 was an effective source of phenylalanine dehydrogenase (PDH) for the reaction. For this process formate dehydrogenase (FDH) was used for regeneration of NADH. Candida boidinii grown on methanol was the initial source for the FDH. Although both the glucose and formate dehydrogenase reactions are equally effective for regeneration of NADH, the easy removal of C 0 compared to 2


In Asymmetric Synthesis and Application of -Amino Acids; Soloshonok, V., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2009. 3

2

-

2

2

H 0 + l/ 0

2

gluconolactone

Figure 3. Preparation of L-6-hydroxynorleucine from 5-(4-hydroxybutyl) hydantoin

+ NH

2

+H 0

catalase

glucose


312


3 ammonium formate

formate dehydrogenase • CO

Figure 4. Conversion of keto acid acetal 3 to amino acid acetal 4. Phenylalanine dehydrogenase catalyzes reductive amination of the keto acid. Formate dehydrogenase is usedfor regeneration of NADH.

gluconic acid made this a preferable method for isolation of the amino acid product by direct crystallization from water/methanol. T. intermedius IFO14230 (ATCC 33205) was first identified as a source of PDH by Ohshima et al(28). The enzyme was purified and characterized (28) then cloned and expressed in E. coli by the same workers (32). The enzyme was reported to be moderately specific for deamination of phenylalanine and to carry out the amination of some keto acids at a much lower rate than amination of phenylpyruvate (28) In our screening, the enzyme was the most effective amino acid dehydrogenase identified for the reductive amination of the keto acid acetal. Wet cells, heat-dried cells, extracts and immobilized enzymes were all useful for the reaction, but heat-dried cell preparations were the simplest and most convenient enzyme source to use. Heat-dried cells were produced by drying the cells under vacuum at 54 °C, then milling to 98%. The procedure with P. pastoris was also scaled up to produce 15.5 kg of 4 in 97 M % yield and ee >98% in a 180-L batch using 10% keto acid concentration. Subsequent to this work the Pichia pastoris FDH was cloned and expressed in E. coli together with the 7! intermedius PDH to allow both enzymes to be induced with β-isopropyl-thio-Dgalactoside (IPTG) (36). The route using the amino acid acetal 4 for preparation of the bicyclic intermediate for Vanlev is summarized in Figure 5. The amino acid acetal was converted to the dimethyl acetal methyl ester, then coupled with N-protected homocystine to give a dipeptide dimer. The dimer was converted to the monomer with dithiothreitol or tributylphosphine. Acidification of the monomer gave the aldehyde which cyclized to the bicyclic intermediate with concomitant hydrolysis of the ester.

L-3-Hydroxyadamantylglycine L-3-Hydroxyadamantylglycine (6) is an intermediate required for the dipeptidyl peptidase-IV inhibitor, Saxagliptin, a drug candidate for treatment of Type-2 diabetes (Figure 6). This amino acid was originally prepared using an asymmetric Strecker amino acid synthesis (37). For an alternative route,



Figure 5. Conversion of amino acid acetal to the bycyclic intermediate



*-

C0 2

r

2

v

H N

u

CN

Saxagliptin

Ο

BocHN

HO

HO 7

Figure 6. Preparation of S-3-hydroxyadamantylglycine, an intermediate for Saxagliptin (BMS-477118)

ammonium formate

HO 5

^ NADH NAD ^ — ^ formate dehydrogenase

phenylalanine dehydrogenase


316 3' end of native PDH gene and corresponding amino acids AAC

AGC GCA AGG AGG TAA

Asn

Ser

Ala

Arg

Arg

Stop


3' end of PDHmod gene and corresponding amino acids (changed or new amino acids in bold): AAC

AGC GCG GAG GGG TAC CTC GAG CCG CGG

Asn

Ser

Ala

Glu

Gly

Tyr

Leu

Glu

CGG

CCG CGA ATT AAT TCG CCT TAG

Arg

Pro

Arg

He

Asn

Ser

Pro

Pro

Arg

Stop

Figure 7. Comparison of 3 ' ends of native pdh gene with modified gene re isolatedfrom Pichia pastoris SCI 6176 (Reproduced with permission from reference 36. Copyright 2007 Wiley-VCH Verlag GmbH and Company.)

screening of amino acid dehydrogenases indicated that the recombinant phenylalanine dehydrogenase from Thermoactinomyces intermedius expressed in Pichia pastoris SC16176 previously used to prepare the amino acid acetal 4 was also the most effective enzyme for reductive amination of keto acid 5 (36). in this case cell extract was much more effective than the heat-dried cells, in contrast to the results for the reductive amination of 3. The more bulky substrate 5 may have difficulty in entering cells. Surprisingly the enzyme expressed in Pichia pastoris was much more effective than the enzyme expressed in E. coli even when the activity of the enzyme from E. coli (assayed with phenylpyruvate as substrate) was much higher than that expressed in Pichia. After reisolation of the pdh gene from Pichia pastoris SC16176 and comparison with the original published sequence, this anomaly was found to be due to a modification of the original enzyme that had inadvertently been introduced during the cloning procedure. This modification consisted of 2 amino acid changes at the Cterminus and a 12-amino acid extension of the C-terminus (Figure 7). The modified enzyme was more effective with keto acid 5 than the original enzyme but had a lower specific activity than the original enzyme with phenylpyruvate. In addition the heat stability of the modified enzyme was decreased, with all activity lost after 1 h at 60 °C compared to complete activity loss after 1 h at 70 °C for the original enzyme. Since the reaction was run at 40 °C to accomodate the lower stability of formate dehydrogenase, this change was of little consequence.


317 Production of multi-kg batches of L-3-hydroxyadamantylglycine was originally carried out with extracts of Pichia pastoris SC16176 containing the modified phenylalanine dehydrogenase (PDHmod) inducible with methanol together with the endogenous FDH produced during growth of the cells on methanol. The isolated yield (using Dowex 50 (H )) of the amino acid was 96% with ee >99%. Later, for further scaleup of the production of 6, PDHmod from Pichia pastoris SCI 6176 was expressed in E. coli together with FDHfromPichia pastoris with both enzymes under the control of the tac promoter inducible by IPTG. With sufficiently pure keto acid substrate, the process was carried out at 10% keto acid concentration. The Boc-protected amino acid 7 is the required intermediate for the synthetic route, and amino acid 6 was converted directly to the Bocderivative before isolation, then isolated by an extraction procedure. To support the development of Saxagliptin, more than 1000 kg of intermediate 7 has been prepared using this enzymatic process.


+

Modification of Amino Acid Dehydrogenases to Change Substrate Specificity Although the modification of PDH to produce an enzyme more effective for preparation of L-3-hydroxyadamantylglycine was introduced inadvertently, enzyme engineering and directed evolution have been applied to amino acid dehydrogenases to change the substrate specificities. A hexapeptide sequence believed to be important for substrate recognition in PDH from Thermoactinomyces intermedius was replaced with the corresponding sequence from the leucine dehydrogenase of Bacillus stearothermophilus by Soda and coworkers (38) Activities were decreased for both aromatic and aliphatic amino acids and keto acids compared to the wild-type enzyme although the decreases were larger for the aromatic substrates. In addition the altered enzyme was found to be a monomer/dimer mixture in contrast to the hexamer structure of the original enzyme. This group also created a chimeric enzyme by combining the amino-terminal domain of PDH from Thermoactinomyces intermedius with the carboxy-terminal domain of leucine dehydrogenase from Bacillus stearothermophilus (39) The chimeric enzyme had a broader substrate specificity that was a mixture of the specificities from the two parent enzymes, although lower activity compared to the parent enzyme with the preferred substrates of each of the parent enzymes. Engel and coworkers used site directed mutagenesis based on structural analysis to construct single and double mutants with G124A and L307V changes in PDH from Bacillus sphaericus with the amino acid replacements being the corresponding amino acids from leucine dehydrogenase. K / K for phenylpyruvate was decreased for all three mutant enzymes but increased for cat


m


318 aliphatic keto acids, with almost a 100-fold increase in k^/Km for ct-keto valerate in the double mutant compared to the wild type (40) Three other mutants of B. sphaericus PDH with substitutions at Ν145 had improved activity compared to the wild type with some keto acids but less activity with others (41) and were used for preparation of three p-substituted L-phenylalanine derivatives (42). The L307V mutant was also used for the synthesis of a p-substituted Lphenylalanine (43). All of the naturally occurring amino acid dehydrogenases with wide substrate specificity described to this time convert keto acids exclusively to the the L-enantiomers. However D-amino acid dehydrogenases have recently been developed by Novick and coworkers (44). Their approach was to start with /w&so-diaminopimelic D-dehydrogenase from Corynebacterium glutamicum, an enzyme with strict D-specificity but limited substrate range, and use directed evolution to broaden the substrate range of the enzyme while preserving the Dselectivity. After five mutations from three rounds of mutagenesis and screening they achieved the desired result of an enzyme able to produce a variety of Damino acids with high ee from ct-keto acid precursors. In this case the enzyme requires NADPH as cofactor and glucose dehydrogenase was used for cofactor regeneration.

Conclusion α-Amino acids are useful synthons for preparing many compounds with pharmacological activity. Reductive amination of α-keto acids using amino acid dehydrogenases is a technology that has been widely applicable at Bristol-Myers Squibb in various synthetic routes. In addition to the examples above, similar procedures were used to prepare six other non-proteinogenic amino acid intermediates, including a D-amino acid (45) The preparation of the keto acid substrates are described in the references for the examples cited. Addition of a Grignard reagent containing the amino acid R- group to diethyloxalate followed by saponification is a useful procedure (27,31). Oxidation of a methyl ketone (10) and hydrolysis of an α,α-dichloro ester are other effective methods (46). In cases where synthesis of the keto acid is difficult, another approach is to prepare the racemic amino acid by chemical methods, treat with a D- or L-amino acid oxidase (27,47) to convert the unwanted enantiomer to the keto acid and then treat the mixture with an L- or D-amino acid dehydrogenase to convert the mixture entirely to the desired enantiomer.

References 1

May, O.; Verseck, S.; Bommarius, Α.; Drauz K. Org. Proc. Res. & Dev. 2002, 6, 452-457.


319 2. 3. 4.


5. 6. 7. 8.

9. 10. 11. 12.

Altenbuchner, J.; Siemann-Herzberg, M . ; Syldak, C. Curr. Opin. Biotechnol. 2001, 12, 559-563. Drauz, K. Chimia 1997, 51, 310-314. Pietzsch, M . ; Syldatk, C. in Enzyme Catalysis in Organic Synthesis (2 Edition); Drauz, K.; Waldmann, H., Eds.; Wiley-VCH: Weinheim, Germany 2002; Vol. 2, pp 761-799. Moriguchi, M.; Ideta, K. Applied Environ. Microbiol. 1988, 54, 2767-2770 Komeda, H.; Asano, Y. Eur. J. Biochem. 2000, 267, 2028-2035. Yamaguchi, S.; Komeda, H.; Asano, Y. Appl. Environ. Microbiol. 2007, 73, 5370-5373. Bennett, D. J.; Buchanan, Κ. I.; Cooke, Α.; Epemolu, O.; Hamilton, N . M.; Hutchinson, E. J.; Mitchell, A. J. Chem. Soc., Perkin Trans. 1 2001, 362-365. Miyazawa, T.; Iwanaga, H.; Yamada, T.; Kuwata, S. Biotechnol. Lett. 1994, 16, 373-378. Larionov, Ο. V.; de Meijere, A. Adv. Synth. Catal. 2006, 348, 1071-1078. Taylor, P. P.; Pantaleone, D. P.; Senkpeil, R. F.; Fotheringham, I. G. TrendsBiotechnol.1998, 16, 412-418. Rozzell, J. D.; Bommarius, A. S. in Enzyme Catalysis in Organic Synthesis (2 Edition); Drauz, K.; Waldmann, H., Eds.; Wiley-VCH: Weinheim, Germany 2002; Vol. 2, pp 873-893. Bommarius, A. S in Enzyme Catalysis in Organic Synthesis (2 Edition); Drauz, K.; Waldmann, H., Eds.; Wiley-VCH: Weinheim, Germany 2002; Vol 3, pp 1047-1063. Ohshima, T.; Soda, K. in Stereoselective Biocatalysis, Patel, R. N., Ed.; Marcel Dekker, New York, 2000; pp 877-902. Shaked, Z.; Whitesides, G. M. J. Am. Chem. Soc. 1980, 102, 7104-7105 Kula, M . R.; Wandrey, C. Methods Enzymol. 1987, 136, 9-21. Bommarius, A. S.; Drauz, K.; Hummel, W.; Kula, M . R.; Wandrey, C. Biocatalysis 1994, 10, 31-47. Wong, C-H.; Drueckhammer, D. G.; Sweers, H. M . J. Am. Chem. Soc. 1985, 107, 4028-4031. Weckbecker, Α.; Hummel, W. in Methods in Biotechnology, Microbial Enzymes and Biotransformations; Barredo, J. L., Ed.; Humana Press, Totawa, NJ, 2005; Vol. 17, pp 225-237. Tishkov, V. I.; Galkin, A. G.; Fedorchuk, V. V.; Savitsky, P. Α.; Rojkova, A. M.; Gieren, H.; Kula, M-R. Biotechnol. Bioeng. 1999, 64, 187-193. Serov, E.; Popova, A. S.; Fedorchuk, V. V.; Tishkov, V. I. Biochem J. 2002, 367, 841-847. Walsh, C. Enzymatic Reaction Mechanisms, W. H. Freeman, New York, 1979;p313. van der Donk, W. Α.; Zhao, H. Curr. Opin. Biotechnol. 2003, 14, 421-426. Johannes, T. W.; Woodyer, R. D.; Zhao, H. Biotechnol. Bioeng. 2007, 96, 18-26. nd

nd

13.

14. 15. 16. 17. 18. 19.

20. 21. 22. 23. 24.

nd



320 25. Hanson, R. L.; Singh, J.; Kissick, T. P.; Patel, R. N.; Szarka, L. J.; Mueller, R. H. Bioorg. Chemistry 1990, 18, 116-130. 26. Robl, J. Α.; Sun, C.; Stevenson, J.; Ryono, D. E.; Simpkins, L. M . ; Cimarusti, M . P.; Dejneka, T.; Slusarchyk, W. Α.; Chao, S.; Stratton, L.; Misra, R. N.; Bednarz, M. S.; Asaad, M.M.; Cheung, H. S.; Aboa-Offei, Β. E.; Smith, P.L.; Mathers, P. D.; Fox, M.; Schaeffer, T. R.; Seymour, A. A. ; Trippodo, N. C. J. Med. Chem. 1997, 40, 1570-1577. 27. Hanson, R. L.; Schwinden, M. D.; Banerjee, Α.; Brzozowski, D. B.; Chen, B.-C; Patel, B. P.; McNamee, C. G.; Kodersha, G. Α.; Kronenthal, D. R.; Patel, R. N.; Szarka, L. J. Bioorg. Med. Chem. 1999, 7, 2247-2252. 28. Oshima, T.; Takada, H.; Yoshimura, T.; Esaki, N.; Soda, K. J. Bacteriol. 1991, 173, 3943-3948. 29. Oshima, T.; Nishida, N . ; Bakthavatsalam, S.; Kataoka, K.; Takada, H.; Yoshimura, T.; Esaki, N.; Soda, K. Eur. J. Biochem. 1994, 222, 305-312. 30. Wei,C.;Huang, J.; Tsai, Y.Biotechnol.Bioeng. 1989, 34, 570-574. 31. Hanson, R. L.; Howell, J. M.; LaPorte, T. L; Donovan, M. J.; Cazzulino, D. L.; Zannella, V.; Montana, M. Α.; Nanduri, V. B.; Schwarz, S. R.; Eiring, R. F.; Durand, S. C.; Wasylyk, J. M . ; Parker, W. L.; Liu, M . S.; Okuniewicz, F. J.; Chen, B.-C.; Harris, J. C.; Natalie, K. J.; Ramig, K.; Swaminathan, S.; Rosso, V. W.; Pack, S. K.; Lotz, B. T.; Bernot, P. J.; Rusowicz, Α.; Lust, D. Α.; Tse, K. S.; Venit, J. J.; Szarka, L. J.; Patel, R. N . Enzyme Microb. Technol. 2000, 26, 348-358. 32. Takada, H.; Yoshimura, T.; Ohshima, T.; Esaki, N.; Soda, K. J. Biochem. 1991, 109, 371-376. 33. Schütte, H.; Flossdorf, J.; Sahm, H.; Kula, M-R. Eur. J. Biochem. 1976, 62, 151-160. 34. Hou, C. T.; Patel, R. N.; Laskin, Α. I.; Barnabe, N. Arch. Biochem. Biophys. 1982, 216, 296-305. 35. Allais, J.J.; Louktibi, Α.; Baratti, J. Agric. Biol. Chem. 1983, 47, 2547-2554. 36. Hanson, R. L.; Goldberg, S. L.; Brzozowski, D. B.; Tully, T. P; Cazzulino, D.; Parker, W. L.; Lyngberg, Ο. K.; Vu, T. C.; Wong, M . K.; Patel, R.N. Adv. Syn. Catal. 2007, 349, 1369-1378. 37. Augeri, D. J.; Robl, J. Α.; Betebenner, D. Α.; Magnin, D. R.; Khanna, Α.; Robertson, J. G.; Wang, Α.; Simpkins, L. M.; Taunk, P.; Huang, Q.; Han, S.-P.; Abboa-Offei, B.; Cap, M.; Xin, L.; Tao, L.; Tozzo, E.; Welzel, G. E.; Egan, D. M.; Marcinkeviciene, J.; Chang, S. Y.; Biller, S. Α.; Kirby, M . S.; Parker, R. Α.; Hamann, L. G. J. Med. Chem. 2005, 48, 5025-5037. 38. Kataoka, K.; Takada, H.; Yoshimura, T.; Furuyoshi, S.; Esaki, N.; Ohshima, T.; Soda, K. J. Biochem 1993, 114, 69-75. 39. Kataoka, K.; Takada, H.; Tanizawa, K.; Yoshimura, T.; Esaki, N.; Ohshima, T.; Soda, K. J. Biochem 1994, 116, 931-936. 40. Seah, S. Y . K.; Britton, K. L.; Rice, D. W.; Asano, Y.; Engel, P. C. Eur. J. Biochem. 2003, 270, 4628-4634. 41. Busca, P.; Paradisi, F.; Moynihan, E.; Maguire, A. R.; Engel, P. C. Org. Biomol. Chem. 2004, 2, 2684-2691.


321


42. Paradisi, F.; Collins, S.; Maguire, A. R.; Engel, P. C. J. Biotechnol. 2007, 128, 408-411. 43. Chen, S.; Engel, P. C. Enz. Microb. Technol. 2007, 40, 1407-1411. 44. Vedha-Peters, K.; Gunawardana, M.; Rozzell, J. D.; Novick, S. J. J. Am. Chem. Soc. 2006, 128, 10923-10929. 45. Hanson, R. L. Bristol-Myers Squibb, unpublished results. 46. Godfrey, J.D.; Fox , R. T.; Buono, F. G.; Gougoutas, J. Z.; Malley, M. F. J. Org. Chem., 2006, 71, 8647-8650. 47. Massad, G.; Zhao, H.; Mobley, H. L. T. J. Bacteriol. 1995, 177, 5878-5883.


Asymmetric Synthesis and Application of Î±-Amino Acids - American

Recommend Documents