Preparation of Chiral Building Blocks by Biochemical Methods

Chapter 24

Preparation of Chiral Building Blocks by Biochemical Methods

Downloaded by FUDAN UNIV on April 26, 2017 | http://pubs.acs.org Publication Date: January 1, 1989 | doi: 10.1021/bk-1989-0389.ch024

Kenji Mori Department of Agricultural Chemistry, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113, Japan Microbial or enzymatic preparations of the chiral building blocks useful in organic synthesis are reviewed. Conversions of these chiral building blocks to important bioactive natural products are also illustrated. In s p i t e o f t h e r e m a r k a b l e p r o g r e s s i n t h e f i e l d o f c h e m i c a l asymmetric synthesis m i c r o b i a l o r enzymatic processes a r e s t i l l a t t r a c t i v e t o p r e p a r a t i v e c h e m i s t s who w a n t t o s y n t h e s i z e e n a n t i o m e r i c a l l y pure b i o a c t i v e n a t u r a l p r o d u c t s i n amounts s u f f i c i e n t f o r extensive b i o l o g i c a l evaluation. S i n c e t h e p u b l i c a t i o n i n 1976 o f a s t a n d a r d r e f e r e n c e b o o k b y Jones, S i h and P e r l m a n (2), an i n c r e a s i n g number o f o r g a n i c c h e m i s t s has become i n v o l v e d i n s t u d i e s on t h e a p p l i c a t i o n o f b i o c h e m i c a l systems i n o r g a n i c c h e m i s t r y . T h e i r approach i s o f t e n d i f f e r e n t f r o m t h a t by b i o c h e m i s t s , because o r g a n i c c h e m i s t s a r e much more aware o f the g e n e r a l u t i l i t y o f a c h i r a l b u i l d i n g b l o c k o b t a i n a b l e by a p a r t i c u l a r biochemical reaction. Our team a t t h e U n i v e r s i t y o f Tokyo h a s pursued, o v e r a decade, b i o c h e m i c a l methods l e a d i n g t o v e r s a t i l e c h i r a l b u i l d i n g b l o c k s f o r o r g a n i c s y n t h e s i s (3). T h i s paper summarizes o u r r e c e n t work on t h e subject. 0t-Amino A c i d s as C h i r a l B u i l d i n g B l o c k s E n a n t i o m e r i c a l l y p u r e α-amino a c i d s c a n r e a d i l y be p r e - p a r e d by r e s o l v i n g ( i ) - N - a c e t y l (or c h l o r o a c e t y l ) - a - a m i n o a c i d w i t h amino acylase of Aspergillus origin. T h i s m i c r o b i a l enzyme i s unexpensive, s t a b l e , and o f b r o a d s u b s t r a t e s p e c i f i c i t y a l l o w i n g t h e r e s o l u t i o n o f α-amino a c i d s w i t h a b r a n c h e d - o r a l o n g - c h a i n a l k y l group. α-Amino A c i d I t s e l f a s a B u i l d i n g B l o c k - S y n t h e s i s o f G i z z e r o s i n e . A d i s e a s e named " b l a c k v o m i t " i s a b i g p r o b l e m i n p o u l t r y i n d u s t r y . The d i s e a s e i s a c c o m p a n i e d b y g i z z a r d e r o s i o n o r u l c e r a t i o n i n c h i c k s , a n d known t o be c a u s e d b y b r o w n f i s h m e a l i n t h e d i e t . I n 1983 O k a z a k i e t a l . i s o l a t e d 2 mg o f a t o x i c compound f r o m 10 k g o f h e a t e d m a c k e r e l meal. The t o x i n c a u s e d s e v e r e g i z z a r d e r o s i o n i n c h i c k s w i t h i n a week when f e d t o t h e m a t t h e l e v e l o f c a . 50 y g / d a y

c

0097-6156/89/0389-0348$06.00/0 1989 American Chemical Society

Whitaker and Sonnet; Biocatalysis in Agricultural Biotechnology ACS Symposium Series; American Chemical Society: Washington, DC, 1989.


24.

MORI

Preparation of Chiral Building Blocks

349

(4) . T h i s t o x i n was named g i z z e r o s i n e and a s s i g n e d s t r u c t u r e 1 w i t h unknown a b s o l u t e c o n f i g u r a t i o n ( 4 ) . Our s y n t h e s i s o f (±)-l by t h e r e d u c t i v e c o u p l i n g o f h i s t a m i n e d i h y d r o c h l o r i d e (2) and an a l d e h y d e 3 c o n f i r m e d t h e proposed s t r u c t u r e (5). To c l a r i f y t h e a b o s l u t e c o n f i g u r a t i o n o f g i z z e r o s i n e , i t s e n a n t i o m e r s w e r e s y n t h e s i z e d a s shown i n F i g u r e 1. R e s o l u t i o n o f ( ± ) - 4 a w i t h a m i n o a c y l a s e s m o o t h l y y i e l d e d ( S ) - 4 b and ( R ) - 4 a . Only (5) - l was found t o be t o x i c when f e d t o c h i c k s (6). α-Hydroxy A c i d and Epoxide as B u i l d i n g B l o c k s . D e a m i n a t i o n o f an ga m i n o a c i d w i t h n i t r o u s a c i d i s known t o g i v e t h e c o r r e s p o n d i n g g hydroxy a c i d w i t h r e t e n t i o n o f c o n f i g u r a t i o n . An g-hydroxy a c i d can be c o n v e r t e d t o an e p o x i d e . B o t h g - h y d r o x y a c i d s and e p o x i d e s a r e v e r s a t i l e c h i r a l b u i l d i n g b l o c k s i n n a t u r a l p r o d u c t s s y n t h e s e s (30· A l c o h o l as a C h i r a l B u i l d i n g B l o c k V a r i o u s l i p a s e s and e s t e r a s e s a r e u s e d f o r t h e p r e p a r a t i o n o f o p t i c a l l y a c t i v e a l c o h o l s , w h i c h can s e r v e as c h i r a l b u i l d i n g b l o c k s . ( l S , 4 R ) - 4 - t - B u t y l d i m e t h y l s i l y l o x y - 3 - c h l o r o - 2 - c y c l o p e n t e n - l - o l as a B u i l d i n g B l o c k f o r P u n a g l a n d i n 4. P u n a g l a n d i n 4 (PUG 4, F i g u r e 2) i s one o f the c h l o r i n a t e d m a r i n e p r o s t a n o i d s i s o l a t e d f r o m the H a w a i i a n o c t o c o r a l T e l e s t o r u s e i by S c h e u e r e t a l . ( 2 ) · In our s y n t h e s i s of PUG 4, t h e key c h i r a l b u i l d i n g b l o c k 9 was p r e p a r e d by t r e a t i n g a s t e r e o i s o m e r i c m i x t u r e of 8 w i t h p i g p a n c r e a t i c l i p a s e (PPL)(8). F o r t u i t o u s l y , t h e d e s i r e d s t e r e o i s o m e r 9 o f 100% e.e. was t h e o n l y p r o d u c t (25% y i e l d ) o f P P L - c a t a l y z e d h y d r o l y s i s . O x i d a t i o n o f 9 gave 10, w h i c h was s u b s e q u e n t l y c o n v e r t e d t o PUG 4(8). ( R ) - 2 - Ace t o x y me t h y 1-3 -pheny 1 - 1 - p r o p a n o l a s a B u i l d i n g B l o c k f o r Af a c t o r . A - f a c t o r ( 1 4 , F i g u r e 3) i s t h e i n d u c e r o f t h e b i o s y n t h e s i s o f s t r e p t o m y c i n i n i n a c t i v e mutants o f S t r e p t o m y c e s g r i s e u s (9). I t also induces the formation of spores in asporophological m o d i f i c a t i o n s o f £u g r i s e u s (9). Our f i r s t c h i r a l s y n t h e s i s o f 14 employed ( S ) - p a r a c o n i c a c i d (13) as t h e key i n t e r m e d i a t e , w h i c h was o b t a i n e d by the c o n v e n t i o n a l o p t i c a l r e s o l u t i o n (10,11). We r e c e n t l y d e v e l o p e d a r o u t e i n w h i c h (S)-13 was p r e p a r e d by an e n z y m a t i c p r o c e s s ( M o r i , K.; C h i b a , N., The U n i v e r s i t y o f T o k y o , u n p u b l i s h e d d a t a ) . T r e a t m e n t o f d i a c e t a t e 11 w i t h PPL gave (R)-12 o f 86% e.e. C o n v e r s i o n o f ( R ) - 1 2 t o ( S ) - 1 3 was f o l l o w e d by i t s p u r i f i c a t i o n a s an a m i n e s a l t t o g i v e p u r e ( S ) - 1 3 , w h i c h was converted i n s e v e r a l steps to A-factor (14). β-Hydroxy E s t e r s as C h i r a l B u i l d i n g B l o c k s Due t o t h e i r b i f u n c t i o n a l n a t u r e , β - h y d r o x y e s t e r s a r e v e r s a t i l e b u i l d i n g b l o c k s i n o r g a n i c s y n t h e s i s as d e t a i l e d below. P r e p a r a t o n o f t h e E n a n t i o m e r s o f E t h y l 3-Hydroxybutanoate. Reduction o f e t h y l a c e t o a c e t a t e w i t h y e a s t y i e l d s e t h y l (S)-3-hydroxybutanoate (15) a s shown i n F i g u r e 4 ( 1 2 - 1 4 ) . P u r i f i c a t i o n o f c r u d e 15 a s i t s c r y s t a l l i n e 3 , 5 - d i n i t r o b e n z o a t e g i v e s (S)-15 o f 100% e.e. (14,15). E t h y l ( R ) - 3 - h y d r o x y b u t a n o a t e (15) o f 100% e.e. i s p r e p a r e d by e t h a n o l y s i s o f p o l y - 3 - h y d r o x y b u t a n o a t e (PHB)(16,17). Seebach e t a l . used PHB g e n e r a t e d by A l c a l i q e n e s eutrophus (16), w h i l e we employed Zoogloea ramigera(15,17). E t h y l 3-Hydroxybutanoate as a B u i l d i n g B l o c k f o r S u l c a t o l and P i t y o l . ( S ) - S u l c a t o l (16, F i g u r e 5) i s t h e a g g r e g a t i o n pheromone of G n a t h o t r i c h u s r e t u s u s . T h i s was s y n t h e s i z e d i n 73% o v e r a l l y i e l d f r o m ( S ) - 1 5 a s shown i n F i g u r e 5 (13,18). S u l c a t o l (16) was c o n v e r t e d t o p i t y o l (17) by t r e a t m e n t w i t h t h a l l i u m ( I I I ) t r i a c e t a t e . P i t y o l (17) is a male-specific a t t r a c t a n t of the bark b e e t l e P i t y o p h t h o r u s p i t y o q r a p h u s ( 18).


350

BIOCATALYSIS IN AGRICULTURAL BIOTECHNOLOGY

H

H

H 0 C ^ X

NHAc

C

2

NHC0CH Cl


H

H

2

f)

C0 Bn •

C0,Bn

2

H

NHC0 Bn 2

2

(S)-£ COo

+ 2

L

>

NHC0 Bn

H'

(S)-£

H

2

e)

b,c,d)

O H C ^ O ^

NHCOCH Cl

(R)-4a

(S)-Afe

(±)-4q

(S)-4b

° 2

H NH

2

NHC0 Bn 2

H

(S)-2

(SH-2HCI

F i g u r e 1. S y n t h e s i s o f g i z z e r o s i n e . Reagents: a) A s p e r g i l l u s amino acylase, 37 °C, 48 h; b) CbzCl/toluene, NaOH aq-An (92%); c) CS2CO3/DMF; d) BnBr/DMF (45%); e) BH THF ( 8 3 % ) ; f ) (COCl) /DMSO-CH Cl2, E t N (quant.); g) NaBH CN, MS 3A /MeOH (69%); h) H /Pd-C/EtOH; i ) d i l HC1, Recrystallization from MeOH (33%). 3

o

2

2

3

3

2

OSi

4-

V OAc

4+

CI

OAc

b)

>

V ÔH

9

8

os'i-f ! I

"A 10

Figure 2. Synthesis of (1 S,4R)-4-t-butyldimethylsilyloxy-3chloro-2-cyclopenten-1-ol. Reagents: a) PPL (25%); b) PDC/DMF (91%).


24. MORI

351


C I 0 Et 2

a)

PhCH Br

OAc

b.c)

d)

PhCH —^

PhCH -^

2

2

2

OAc

C0 Et 2

/v^C0 H 2

0

P h C H

A

c

f.g.h.i)

2"K H*'

>

OH

c.d) > 50-70V.

> \À/C0 Me 2

93V. e.e.

\ λ / 0 V

2

Μ ·

V

(R)-18

OH

OH f.c.d)

~40V.' Downloaded by FUDAN UNIV on April 26, 2017 | http://pubs.acs.org Publication Date: January 1, 1989 | doi: 10.1021/bk-1989-0389.ch024

(S).J8 Figure 5. Synthesis of ( S ) - s u l c a t o l and (2R,5S)-pityol. Reagents: a) DHP, TsOH (quant.); b) LAH/ether (89%); c) TSCI/C5H5N (quant.); d) Me2C=CHMgBr Cul/THF (quant.); e) AcOH-THF-H 0, Δ (82%); f ) Tl(OAc) /HBF -An-H20 (99%; 12% after MPLC purification). f

2

OH A/ 2 (SH5 C 0

3

OH

OTHP E t

4

d.e)

a.b.c), OTs

f)

Λ Λ Λ (S)-16 Sulcatol

^0' " f OH (2R,5S)-17 Pityol Figure 6. Preparation of the enantiomers of methyl 3 hydroxypentanoate. Reagents: a) Candida rugosa; b) MeOHH2SO4 (80%); c) 3 5-(02N)9CeH3C02H DMAP, DCC/CH Cl2; r e c r y s t a l l i z a t i o n ; d) KOH/THF-MeOH-H20; e) Saccharomyces cerevisiae (70%); f) I^CX^/MeOH. f

f

2


354


OH ^A^C02Me

a,b,c,d,e )

f) v

0CH2Ph


(R)-18 e

( 93 / e.e.) e

QSif

0

m)

I) 20 (1007.e.e.) OH 1

0

OH

1

(1

: 2.8)

OH

0

OH

Γ

(4S,6S,7S)-19

(4R,6S,7S)-19

Figure 7. Synthesis of (4S,6S,7S)-serricornin. Reagents: a) LDA, Mel; b) DHP, PPTS (61% from 18); c) LAH (99%); d) NaH, P h C H C l (94%); e) TsOH, MeOH (quant.); f ) , 3,5(02N)2C6H C02H, PI13P, Et02CN=NC02Et, r e c r y s t a l l i z a t i o n (40%); g) KOH (95%); h) t-BuMe2SiCl, imidazole (quant.); i ) H /Pd-C (97%), j ) T s C l 7 c H N ; k) Nal (99.6%, 2 steps); 1) Et200, LDA (80%); m) AcOH-THF-H 0 (43%). 2

3

2

5

5

2



24. MORI

355


Ο

Ο

OSi-|-

(+)-23 Sporogen-AO 1

Figure 8. Synthesis o f (+)-sporogen-AO 1. Reagents: a) baker's yeast (74%); b) DHP, PPTS (quant.); c) LAH/ether (98%); d) TsCl/C5H5N (95%); e) PPTS/MeOH; f ) aq HC104~ether (85%); g) t-BuOK/t-BuOH (78.5%); h) Ph P, Et0 CN=NC02Et, PhC02H/THF; LiOH/MeOH (80%); i ) t-BuMe SiCl, imidazole-DMF (quant.); j ) Li/NH -t-BuOH, M e l (83%); k) M e S i I (Me Si)2NH; CH2=CHCOMe B F OEt2/i-PrOH-MeN0 (68%); 1) p y r r o l i d i n e / C H (78.6%); m) LDA, MeCHO (92%); n) (COCl)2, DMSO E t N (78.5%); o) DDQ/ether (83%); p) t-BuOOH-Triton Β (70%); q) Me SiCH MgCl; H2SO4-THF; HF-MeCN (88%). 3

2

2

3

3

3

f

6

f

3

2

6

3

3

2


r


356


Figure 9. Synthesis of the enantiomers of p o l y g o d i a l . Reagents: a) baker's yeast (63-79%); b) t-BuMe SiCl (81%); c) LDA/THF-HMPA, Mel (89%); d) NaC=CH/liq NH (99%); e) CuSO^xylene, Δ (51%); f ) H /Pd-CaC03, q u i n o l i n e i n npentane (quant.); g) Me0 CC=CC0 Me, 110°C, 30 h (97%); h) aq HF-MeCN (27% of 27 and 27% of 28 after MPLC); i ) DBU/THF, Δ; H /Pd-C (80% from 27); j ) TfC1-DMAP/CH C1 (86%); k) H /Pd (89%); 1) LAH/ether (82%); m) (C0C1) , DMSO Et3N/CH Cl (63%); n) DBU/THF 2

3

2

2

2

2

2

2

2

2

f

Figure 10. Synthesis of juvenile hormones I and II.


2

2


24. MORI

357


B a e y e r - V i l l i g e r o x i d a t i o n r e a c t i o n t o cleave the cyclohexane r i n g (31). ( 2S, 3S ) - 2 - E t h y 1 - 3 - h y d r o x y - 2 - m e t h y l c y c l o h e x a n o n e a s a B u i l d i n g B l o c k f o r J u v e n i l e Hormones I a n d I I . R e d u c t i o n o f a p r o c h i r a l 1,3d i k e t o n e 30 w i t h P i c h i a t e r r i c o l a KI 0117 f u r n i s h e s (2S,3S)-31 o f 99% e.e. (32). As shown i n F i g u r e 10, 31 was e m p l o y e d a s t h e s t a r t i n g m a t e r i a l f o r the s y n t h e s i s o f e n a n t i o m e r i c a l l y pure (+)-juvenile h o r m o n e s I a n d I I (32). P u r i f i c a t i o n o f 3 1 was a c h i e v e d by r e c r y s t a l l i z a t i o n o f 3 2 , whose B a e y e r - V i l l i g e r o x i d a t i o n g a v e a c r y s t a l l i n e l a c t o n e 33. M e t h a n o l y s i s o f t h e l a c t o n e 33 was f o l l w e d by p r o t e c t i o n o f the g l y c o l system t o g i v e 34. T h i s was c o n v e r t e d t o j u v e n i l e hormones I (35) and I I (36). ( I S , 4 R , 5 S ) - 5 - H y d r o x y - l - m e t h y l b i c y c l o [ 2 . 2 . 1 ]heptan-3-one as a B u i l d i n g B l o c k f o r G l y c i n o e c l e p i n A. R e d u c t i o n o f l - m e t h y l b i c y c l o [ 2.2.1 ] heptane-3,5-dione (37) w i t h baker's y e a s t g i v e s (lS,4R,5S)-5-hydroxyl - m e t h y l b i c y c l o [ 2 . 2 . 1 ] h e p t a n - 3 - o n e (38) o f 8 0 - 8 7 % e.e. a s shown i n F i g u r e 11 ( M o r i , K.; W a t a n a b e , H., T h e U n i v e r s i t y o f T o k y o , unpublished data). By e m p l o y i n g two β-hydroxy ketones 25 and 38 a s t h e b u i l d i n g b l o c k s , g l y c i n o e c l e p i n A (40) was s y n t h e s i z e d v i a 3 9 ( M o r i , K.j Watanabe, H., t h e U n i v e r s i t y o f T o k y o , u n p u b l i s h e d d a t a ) . G l y c i n o e c l e p i n A i s a degraded t r i t e r p e n o i d w i t h s i g n i f i c a n t h a t c h s t i m u l a t i n g a c t i v i t y f o r t h e soybean c y s t nematode (33, 34).

CÛ2H Glycinoeclepin A 40

Figure 11.

Synthesis of glycinoeclepin A.

Acknowledgments I thank my co-workers whose names appear i n t h e r e f e r e n c e s f o r t h e i r e n t h u s i a s m i n c a r r y i n g o u t t h e b i o c h e m i c a l and s y n t h e t i c works. F i n a n c i a l s u p p o r t o f t h i s p r o j e c t by Japanese M i n i s t r y o f E d u c a t i o n , S c i e n c e and C u l t u r e i s acknowledged w i t h thanks.

Literature Cited

1. 2.

Morrison, J.D., Ed. Asymmetric Synthesis Vols. Academic Press: Orlando, 1983-1985. Jones, J.B.; Sih, C.J.; Perlman, D., Eds. Application Biochemical Systems in Organic Chemistry Part 1; Wiley: New York, 1976.


1-5; of John

358 3. 4. 5. 6. 7.


8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34.


Mori, K. In Studies in Natural Products Chemistry Vol. 1; Rahman, A.-u., Ed.; Elsevier: Amsterdam, 1988. Okazaki, T.; Noguchi, T. Igarashi, K.; Sakagami. Y.; Seto, H.; Mori, K.; Naito, H.; Masumura, T.; Sugahara, M. Agric. Biol. Chem. 1983, 47, 2949. Mori,K.; Okazaki, T.; Noguchi, T.; Naito, H. Agric.Biol.Chem. 1983, 47, 2131. Mori, K.; Sugai, T.; Maeda, Y.; Okazaki, T.; Noguchi, T.; Naito, H. Tetrahedron 1985, 41, 5307. Baker, B.J.; Okuda, R.K.; Yu, P.T.K.; Scheuer, P.J. J.Am. Chem. Soc. 1985, 107, 2976. Mori, K.; Takeuchi, T. Tetrahedron 1988, 44, 333. Kleiner, E.M.; Pliner, S.A.; Soifer, V.S.; Onoprienko, V.V.; Blasheva, T.A.; Rozynov, B.V.; Khokhlov, A.S. Bioorg. Khim. 1976, 2, 1142. Mori, K.; Yamane, K. Tetrahedron 1982, 38, 2919. Mori, K. Tetrahedron 1983, 39, 3107. Deol, B.S.; Ridley, D.D.; Simpson, G.W. Aust. J. Chem. 1976, 29, 2459. Mori, K. Tetrahedron 1981, 37, 1341. Hungerbuhler, E; Seebach, D.; Wasmuth, D.S.; Helv. Chim. Acta 1981, 64, 1467. Sugai, T. Fujita, M.; Mori, K. Nippon Kagaku Kaishi 1983, 1315. Seebach, D.; Zuger, M.F. Helv. Chim. Acta 1982, 65, 495. Mori, K.; Watanabe, H. Tetrahedron 1984, 40, 299. Mori, K.; Puapoomchareon, P. Liebigs Ann. Chem 1987, 271. Hasegawa, J.; Hamaguchi,S.;Ogura, M.; Watanabe, K. J. Ferment. Technol. 1981, 59, 257. Mori, K.; Watanabe, H. Tetrahedron 1985, 41, 3423. Mori, K.; Mori, H.; Sugai, T. Tetrahedron 1985, 41, 919. Chuman, T.; Kohno, M.; Kato, K; Noguchi, M. Tetrahedron Lett. 1979, 2361. Kitahara, T.; Mori, K. Tetrahedron Lett. 1985, 26, 451. Tanaka, S.; Wada, K.; Marumo, S.: Hattori, H. Tetrahedron Lett 1984, 25, 5907. Mori, K.; Tamura, H. Liebigs Ann. Chem. 1988, 97. Kitahara, T.; Kurata, H.; Mori, K. Tetrahedron 1988, 43, 4339. Mori, K.; Mori, H. Tetrahedron 1985, 41, 5487. Mori, K.; Watanabe, H. Tetrahedron 1986, 42, 273. Barnes, C.S.; Loder, J.W. Aust. J. Chem. 1962, 15, 322. Kubo, I.; Lee, Y.-W.; Pettei, M.; Pilkiewicz, F.; Nakanishi, K. J. Chem. Soc., Chem. Commun. 1976, 1013. Mori, K.; Mori, H. Tetrahedron 1987, 43, 4097. Mori, K.; Fujiwhara, M. Tetrahedron 1988, 44, 343. Masamune,T.;Anetani, M; Fukuzawa, A.; Takasugi, M.; Matsue, H.; Kobayashi, K.; Ueno, S.; Katsui, N. Bull. Chem. Soc. Jpn. 1987, 60, 981. Masamune,T.;Fukuzawa, A.; Furusaki, A.; Ikura, M.; Matsue, H.; Kaneko, T.; Abiko, A.; Sakamoto, N.; Tanimoto, N.; Murai, A. Bull. Chem. Soc. Jpn. 1987, 60. 1001.

RECEIVED

September 19, 1988


Preparation of Chiral Building Blocks by Biochemical Methods

Recommend Documents