Novel Enzymatic Synthesis of 4-O-Cinnamoyl Quinic and Shikimic Acid Derivatives

Transcription

1 Revised: May 003 Novel Enzymatic Synthesis of --Cinnamoyl Quinic and Shikimic Acid Derivatives Nuria Armesto, Miguel Ferrero, Susana Fernández, and Vicente Gotor* Departamento de Química rgánica e Inorgánica, Facultad de Química, Universidad de viedo, 3300-viedo, Spain VGS@sauron.quimica.uniovi.es SUPPLEMENTARY MATERIAL (page of pages) Table of Contents - General Spectroscopy and Experimental Data: S. - Experimental Procedures and Spectroscopical Data: S - General Procedure for synthesis of vinyl esters 3b c and a b: S. - General Procedure for synthesis of anhydrides 8a e and a b: S3. - Spectroscopical Data of: 3b (S), 3c (S), a (S), b (S3), a (S), 7a (S), 8a (S3), 8b (S3), 8c (S), 8d (S), 8e (S), a (S), b (S), 0e (S), a (S), b (S), c (S7), d (S7), a (S7), b (S8), a (S8), b (S8). - Copy of H and 3 C NMR Spectra of: 3b (S, S0), 3c (S, S), a (S3, S), b (S, S), a (S7, S8), 7a (S, S0), 8a (S, S), 8b (S3, S), 8c (S, S), 8d (S7, S8), 8e (S, S30), a (S3, S3), b (S33, S3), 0e (S3, S3), a (S37, S38), b (S3, S0), c (S, S), d (S3, S), a (S, S), b (S7, S8), a (S, S0), b (S, S). General Spectroscopy and Experimental Data Melting points were taken on samples in open capillary tubes and are uncorrected. IR spectra were recorded on an Infrared Fourier Transform spectrophotometer using KBr pellets or NaCl plates. Flash chromatography was performed using silica gel 0 (30-00 mesh) except for a, 7a, and 0e in which silica 0 Å (3 3 µm) ph 7 was used. The chemical shifts in H and 3 C are given in delta (δ) values and the coupling constants (J) in Hertz (Hz). EI +, ESI +, and APCI + were used to record mass spectra (MS). S

2 Experimental Procedures and Spectroscopical Data Synthesis of vinyl esters 3b c and a b. General procedure. A mixture of carboxylic acid (0 mmol), vinyl acetate (00 ml,.08 mmol), Pd(Ac) (30 mg,. mmol), and KH ( mg, mmol) was stirred at rt for 7 h. The mixture was filtered and the solid residue was washed with vinyl acetate. After evaporation of the vinyl acetate the crude was purified by flash chromatography (gradient eluent 30% EtAc/Hex for 3; 0% EtAc/Hex for a; and % Et /CH Cl for b) to afford 3b (white solid, 7% yield), 3c (white solid, 77% yield), a (colorless oil, 7% yield), and b (yellow oil, 0% yield). Compounds are volatile in the vacuum pump. Vinyl coumarate (3b). R f (30% EtAc/Hexane): 0.3; mp: -3 C; IR (NaCl): υ 303, 303, 8, 70,, 0, 87,,, 0, and 3 cm - ; H NMR (CDCl3, 300 MHz): δ. (dd, H, H, 3 J HH., J HH. Hz),.0 (dd, H, H 0, 3 J HH.0, J HH. Hz),.8 (bs, H, H),.33 (d, H, H, 3 J HH. Hz),.8 (d, H, H, 3 J HH 8.7 Hz), (m, 3H, H +H 8 ), and 7.7 (d, H, H 3, 3 J HH.0 Hz); 3 C NMR (CDCl 3, 7. MHz): δ 8.0 (C ), 3. (C ),.0 (C ),. (C ), 30.3 (C ),. (C 8 ),. (C 3 ), 8. (C 7 ), and. (C ); MS (APCI +, m/z): [(M+H) +, 00%]; Anal. Calcd. (%) for C H 0 3 : C,.; H,.3. Found: C,.; H,.. Vinyl ferulate (3c). R f (30% EtAc/Hexane): 0.3; mp: 8-87 C; IR (NaCl): υ 38, 7, 30, 0,, 3, 07, and 0 cm - ; H NMR (CDCl 3, 300 MHz): δ 3. (s, 3H, Me),. (dd, H, H, 3 J HH.3, J HH. Hz),.7 (dd, H, H, 3 J HH 3., J HH. Hz),.3 (d, H, H, 3 J HH. Hz),.3 (d, H, H 8, 3 J HH 8. Hz), (m, H, H +H ), 7.3 (dd, H, H 0, 3 J HH 3.,.3 Hz), and 7.7 (d, H, H 3, 3 J HH. Hz); 3 C NMR (CDCl 3, 7. MHz):ÀÃδ.8 (Me), 7. (C ), 0. (C ), 3.7 (C ),.7 (C 8 ), 3. (C ),. (C ),. (C 0 ),.7 (C 3 ), 8.3 (C +C 7 ), and. (C ); MS (APCI +, m/z): [(M+H) +, 00%]; Anal. Calcd. (%) for C H : C,.; H,.. Found: C,.; H,.. Vinyl hydrocinnamate (a). R f (30% EtAc/Hexane): 0.7; IR (NaCl): υ 308, 30, 3030, 3, 8, 7,, 7, 3, 7,, 8 cm - ; H NMR (CDCl 3, 300 MHz): δ.7 (t, H, H, 3 J HH 7.7 Hz), 3.0 (t, H, H 3, 3 J HH 7.7 Hz),. (dd, H, H, 3 J HH.3, J HH. Hz),.3 (dd, H, H 0, 3 J HH.0, J HH. Hz), and (m, H, H +H +H 7 +H 8 ); 3 C NMR (CDCl 3, 7. MHz):ÀÃδ 30. (C 3 ), 3. (C ), 7. (C ),.3 (C 7 ), 8., 8. (C +C ), 0.0 (C ),.0 (C 8 ), and.8 Gao, C.; Mayon, P.; MacManus, D. A.; Vulfson, E. N. Biotechnol. Bioeng. 00, 7, 3-3. S

3 (C ); MS (APCI +, m/z): 77 [(M+H) +, 00%]; Anal. Calcd. (%) for C H : C, 7.8; H,.8. Found: C, 7.8; H,.. Vinyl 3-(-hydroxyphenyl)propionate (b). R f (30% EtAc/Hexane): 0.3; IR (NaCl): υ 30, 303, 30, 33, 7,, 3,,,, cm - ; H NMR (CDCl 3, 300 MHz): δ. (t, H, H, 3 J HH 7.7 Hz),.3 (t, H, H 3, 3 J HH 7.7 Hz),.0 (dd, H, H, 3 J HH., J HH. Hz),.0 (dd, H, H 0, 3 J HH.0, J HH. Hz),.77 (d, H, H, 3 J HH 8. Hz), 7.08 (d, H, H, 3 J HH 8. Hz), and 7. (dd, H, H 8, 3 J HH.0,. Hz); 3 C NMR (CDCl 3, 7. MHz):ÀÃδ.7 (C 3 ), 3. (C ), 7. (C ),. (C ),. (C ), 3. (C ),.0 (C 8 ),. (C 7 ), and 70.(C ); MS (EI +, m/z): (M +, %), (), (7), 07 (00), (), and 77 (8); HRMS (m/z) Calcd. for C H 3 :.078. Found:.078. Anal. Calcd. (%) for C H 3 : C, 8.7; H,.. Found: C, 8.; H,.. Synthesis of anhydrides 8a e and a b. General procedure. A solution of carboxylic acid (0 mmol) and Et 3 N (.3 ml, 0 mmol) in EtAc (7 ml) was allowed to react with triphosgene (0 mg,.7 mmol) at 0 C for 0 min and at rt for additional min. The solution was filtered on celite, washed with EtAc, and the filtrate was evaporated to dryness to afford 8a (white crystalline solid, 7% yield), 8b (white solid, 3% yield), 8c (white solid, 3% yield), 8d (white solid, 7% yield), 8e (white crystalline solid, 7% yield), a (white gummy solid, 3% yield), and b (white solid, 7% yield). For 8b, 8c, and a acetylation (Ac /pyridine/dmap) of the phenol group in the carboxylic acid was carried out before anhydride synthesis. Cinnamic anhydride (8a). R f (0% EtAc/Hexane): 0.7; H NMR (CDCl 3, 300 MHz): δ. (d, H, H, 3 J HH.8 Hz), (m, H, H +H 7 ), 7. (m, H, H), and 7.88 (d, H, H 3, 3 J HH.8 Hz); 3 C NMR (CDCl 3, 7. MHz): δ. (C ), 8. (C ),.0 (C ), 3. (C 7 ), 33. (C ), 8. (C 3 ), and. (C ); MS (ESI +, m/z): 30 [(M+Na) +, %], 37 [(M+K) +, 0%], and 7 [(M+Na) +, 00%]; Anal. Calcd. (%) for C 8 H 3 : C, 77.8; H,.07. Found: C, 77.7; H,.. --Acetylcoumaric anhydride (8b). R f (0% EtAc/Hexane): 0.; mp: 3-33 C; IR (NaCl): υ 7, 7, 30, 0, 0, 0,, 0, 3, and 00 cm - ; H NMR (CDCl 3, 300 MHz): δ.3 (s, 3H, Ac),. (d, H, H, 3 J HH. Hz), 7. (d, H, H, 3 J HH 8. Hz), 7. (d, H, H, 3 J HH 8.7 Hz), and 7.8 (d, H, H 3, 3 J HH. Hz); 3 C NMR (CDCl 3, 7. MHz): δ.0 (C ),.0 (C ),. (C ),.7 (C ), 3. (C ), 7. (C 3 ),.7 (C 7 ),. (C ), and 8. (C 8 ); MS (ESI +, m/z): Kocz, R.; Roestamadji, J.; Mobashery, S. J. rg. Chem.,, 3-. S3

4 7 [(M+Na) +, 0%], and 33 [(M+K) +, 00%]; Anal. Calcd. (%) for C H 8 7 : C, 7.0; H,.0. Found: C,.; H,.. --Acetylferulic anhydride (8c). R f (0% EtAc/Hexane): 0.3; mp: C; IR (NaCl): υ 7, 73, 30, 00, 08,, 8, 078, and 0 cm - ; H NMR (CDCl 3, 300 MHz): δ.3 (s, 3H, Ac), 3.0 (s, 3H, Me),.0 (d, H, H, 3 J HH.8 Hz), 7. (m, 3H, H +H 8 +H ), and 7.83 (d, H, H 3, 3 J HH.7 Hz), 3 C NMR (CDCl 3, 7. MHz): δ 0. (C ),. (C 0 ),. (C ),.8 (C ),.8 (C ), 3. (C 8 ), 3. (C ),. (C 7 ), 7. (C 3 ),. (C ),. (C ), and 8. (C ); MS (ESI +, m/z): 77 [(M+Na) +, 7%] and 3 [(M+K) +, 00%]; Anal. Calcd. (%) for C H : C, 3.3; H,.88. Found: C, 3.; H,.. -Methoxycinnamic anhydride (8d). R f (0% EtAc/Hexane): 0.8; mp: 0-0 C; IR (NaCl): υ 303, 3008, 8, 77, 707,, 0,,, 3, 7, and 07 cm - ; H NMR (CDCl 3, 300 MHz): δ 3.0 (s, 3H, Me),. (d, H, H, 3 J HH.7 Hz),. (d, H, H, 3 J HH 8.7 Hz), 7. (d, H, H, 3 J HH 8.7 Hz), and 7.8 (d, H, H 3, 3 J HH.7 Hz); 3 C NMR (CDCl 3, 7. MHz): δ. (C 8 ),.0 (C ),. (C ),. (C ), 30.3 (C ), 8. (C 3 ),. (C 7 ), and. (C ); MS (EI +, m/z): 338 (M +, %), 30 (), (00), 33 (0), and 77 (); HRMS (m/z) Calcd. for C 0 H 8 : Found: Anal. Calcd. (%) for C 0 H 8 : C, 7.0; H,.3. Found: C, 7.; H,.. -Fluorocinnamic anhydride (8e). R f (0% EtAc/Hexane): 0.7; mp: - C; IR (NaCl): υ 77, 7, 3,,,,, and 07 cm - ; H NMR (CDCl 3, 300 MHz): δ.7 (d, H, H, 3 J HH. Hz), 7. (dd, H, H, 3 J HH 8., 3 J HF 8. Hz), 7.0 (dd, H, H, 3 J HH 8., J HF. Hz), and 7.83 (d, H, H 3, 3 J HH. Hz); 3 C NMR (CDCl3, 7. MHz): δ.3 (d, C, C, J CF. Hz),. (C ),. (d, C, C, J CF. Hz), 30. (d, C, C, 3 J CF 8.7 Hz), 7.3 (C 3 ),.3 (C ), and. (d, C, C 7, J CF 3.3 Hz); MS (ESI +, m/z): 33 [(M+K) +, 8%] and 377 [(M+Na) +, 37%]; Anal. Calcd. (%) for C 8 H F 3 : C, 8.7; H, 3.8; F,.0. Found: C, 8.8; H, 3.. -Acetoxycinnamic anhydride (a). R f (0% EtAc/Hexane): 0.; IR (NaCl): υ 307, 38, 77, 7, 8, 03, 83,,, 80, 3, and 07 cm - ; H NMR (CDCl 3, 300 MHz): δ.3 (s, 3H, Ac),. (d, H, H, 3 J HH. Hz), 7.8 (d, H, H, 3 J HH 8. Hz), 7.3 (m, H, H 8 ), 7. (m, H, H 7 ), 7. (dd, H, H, 3 J HH 7., J HH. Hz), 7. (d, H, H 3, 3 J HH.0 Hz); 3 C NMR (CDCl 3, 7. MHz):ÀÃδ 0.7 (C ), 8.3 (C ), 3. (C ),. (C ),. (C 8 ), 7.8 (C ), 3.0 (C 7 ),.8 (C 3 ),. (C ),. (C ), and 8.8 (C 0 ); MS (ESI +, m/z): 7 [(M+Na) +, 00%], and S

5 33 [(M+K) +, 0%]; Anal. Calcd. (%) for C H 8 7 : C, 7.0; H,.0. Found: C, 7.; H,.. -Metoxycinnamic anhydride (b). R f (0% EtAc/Hexane): 0.; mp: 0-0 C; IR (NaCl): υ 3073, 300, 0, 837, 7, 7,,, 88,, 38, and 0 cm - ; H NMR (CDCl 3, 300 MHz): δ 3.3 (s, 3H, Me),.7 (d, H, H, 3 J HH.0 Hz),.-7.0 (m, H, H +H 8 ), 7. (ddd, H, H 7, 3 J HH 8.8, 8.,.7 Hz), 7. (dd, H, H, 3 J HH 7.7,.7 Hz), and 8. (d, H, H 3, 3 J HH.0 Hz); 3 C NMR (CDCl 3, 7. MHz):ÀÃδ. (C 0 ),., 0.7 (C +C 8 ), 7.3 (C ),.7 (C ),. (C ), 3. (C 7 ), 3. (C 3 ), 8.7 (C ), and 3.3 (C ); MS (EI +, m/z): 338 (M +, %), 30 (3), (00), 8 (), and 77 (); HRMS (m/z) Calcd. for C 0 H 8 : Found: Anal. Calcd. (%) for C 0 H 8 : C, 7.0; H,.3. Found: C, 70.; H,.. --Acyl-derivatives from enzymatic acylation: Methyl --cinnamoylshikimate (a). R f (Et ): 0.7; mp: 7- C; IR (KBr): υ 338, 37, 380, 30, 30, 3, 0, 7, 3,, 3, 7, 3, 07, and 08 cm - ; H NMR (CDCl 3, 300 MHz): δ. (dddd, H, H a J HH 8.3, 3 J HH., J HH.8,. Hz),. (dddd, H, H e J HH 8.3, 3 J HH., J HH.,.3 Hz), 3.7 (s, 3H, Me),.37 (m, H, H ),.7 (dd, H, H 3, 3 J HH.0 Hz),. (dd, H, H, 3 J HH 8.,. Hz),. (d, H, H 0, 3 J HH. Hz),. (m, H, H ), (m, 3H, H +H ), 7.3 (m, H, H 3 ), and 7.7 (d, H, 3 J HH.8 Hz); 3 C NMR (CDCl 3, 7. MHz): δ 3.0 (C ),.0 (Me),. (C 3 +C ), 7. (C ), 7. (C 0 ), 8. (C 3 ), 8. (C ),.8 (C ), 30. (C ), 33. (C ), 3. (C ),. (C ),.7, and. 0 (C 7 +C ); [α ] D = - (c., MeH); MS (EI +, m/z): 38 (M +, 7%), 70 (3), 3 (00), 03 (3), and 77 (8); HRMS (m/z) Calcd. for C 7 H 8 : Found: Anal. Calcd. (%) for C 7 H 8 : C,.; H,.7. Found: C,.; H,.. Methyl --hydrocinnamoylshikimate (7a). R f (Et ): 0.3; IR (NaCl): υ 30, 80,, 7,, 7, 3, 38,, 0, 07, and 07 cm - ; H NMR (CDCl 3, 300 MHz): δ. (dddd, H, H a J HH 8.3, 3 J HH., J HH.8,. Hz),.78 (t, 3H, H e +H 0, 3 J HH 7. Hz), 3.0 (t, H, H, 3 J HH 7.7 Hz), 3.78 (s, 3H, Me),. (m, H, H ),. (dd, H, H 3, 3 J HH.0 Hz),.8 (dd, H, H, 3 J HH 8.,. Hz),.8 (m, H, H ), and (m, H, H 3 +H +H ); 3 C NMR (CDCl 3, 7. MHz): δ 30., 30. (C +C ), 3. (C 0 ),. (Me),.7 (C 3 +C ), 7.0 (C ),. (C ), 8., 8. (C 3 +C ),.8 (C ), 3.0 (C ), 3. (C ),. (C 7 ), and 7.8 (C ); 0 [α ] D = -03 (c.3, MeH); MS (ESI +, m/z): 33 [(M+Na) +, 00%], and 3 [(M+K) +, 3%]; Anal. Calcd. (%) for C 7 H 0 : C, 3.7; H,.. Found: C,.0; H,.. S

6 Methyl --(-fluorocinnamoyl)shikimate (0e). R f (Et ): 0.; mp: C; IR (KBr): υ 30, 3073,, 0, 77, 3, 00, 0, 3, 7, 3, 0, 07, and 03 cm - ; H NMR (CDCl 3, 300 MHz): δ. (dddd, H, H a J HH 8., 3 J HH., J HH.8,. Hz),. (dddd, H, H e J HH 8., 3 J HH., J HH.,. Hz), 3.80 (s, 3H, Me),.3 (m, H, H ),.7 (dd, H, H 3, 3 J HH.0 Hz),. (dd, H, H, 3 J HH 8.,. Hz),.3 (d, H, H 0, 3 J HH.3 Hz),. (m, H, H ), 7.0 (dd, H, H, 3 J HH 8., 3 J HF 8. Hz), 7. (dd, H, H 3, 3 J HH 8.7, J HF.3 Hz), and 7.7 (d, H, H, 3 J HH. Hz); 3 C NMR (CDCl 3, 7. MHz): δ 3.0 (C ),. (Me),.,.3 (C 3 +C ), 7.0 (C ),.0 (d, C,C, 3 J CF. Hz),.7 (C 0 ),.8, 30., 30. (m, C, C +C +C 3 ),. (C ),.0 (d, C, C, J CF. Hz), and.7, 0.8 (C 7 +C); [α ] D = -3 (c., MeH); MS (EI +, m/z): 33 (M +, %), (0), (00), (), and 77 (); HRMS (m/z) Calcd. for C 7 H 7 F : Found: Anal. Calcd. (%) for C 7 H 7 F : C, 0.7; H,.0; F,.. Found: C, 0.7; H,.. Methyl --acetylquinate (a). R f (0% MeH/EtAc): 0.3; mp: 8-30 C; IR (KBr): υ 38, 30, 387, 307, 8, 73, 7, 3, 37, 8, and 0 cm - ; H NMR (acetone-d, 300 MHz): δ. (dd, H, H a, J HH 3., 3 J HH 0. Hz),.-. (m, 3H, H +H e ),.0 (s, 3H, H 0 ), 3.7 (s, 3H, Me),. (d, H, H 3, J HH.8 Hz),.-. (m, H, H 3 +H ),.3 (d, H, H, 3 J HH.8 Hz),.7 (dd, H, H, 3 J HH 8.,. Hz), and.00 (s, H, H); 3 C NMR (acetone-d, 7. MHz):À δ.7 (C 0 ), 38. (C ), 3. (C ), 3. (Me),. (C ),. (C 3 ), 7. (C ), 7. (C ), 7. 0 (C ), and 7.3 (C 7 ); [α ] D = - (c., MeH); MS (EI +, m/z): 88 (M + -MeC H, %), 7 (0), (00), and 8 (8); HRMS (m/z) Calcd. for C 8 H : Found: Anal. Calcd. (%) for C 0 H 7 : C, 8.3; H,.. Found: C, 8.3; H,.. Methyl --acryloylquinate (b). R f (EtAc): 0.; mp: - C; IR (KBr): υ 30, 33, 33,, 3, 737, 70,, 0, 38,,, 0, 3, and 073 cm - ; H NMR (acetone-d, 300 MHz): δ. (dd, H, H a, J HH 3.3, 3 J HH 0. Hz),.0-. (m, 3H, H +H e ), 3.7 (s, 3H, Me),. (d, H, H 3, J HH.0 Hz),.-.3 (m, H, H 3 +H ),. (d, H, H, 3 J HH 7.0 Hz),.7 (dd, H, H, 3 J HH 8.8, 3.0 Hz),.03 (s, H, H),.87 (dd, H, H, 3 J HH 0., J HH.7 Hz),.8 (dd, H, H 0, 3 J HH 7.3, 0. Hz), and.0 (dd, H, H, 3 J HH 7.3, J HH.8 Hz); 3 C NMR (acetone-d, 7. MHz):ÀÃδ 3.0 (C ), 3. (C ), 3. (Me),. (C ),. 0 (C 3 ), 7. (C ), 7. (C ), 30. (C 0 ), 3. (C ),. (C ), and 7.3 (C 7 ); [α ] D = - S

7 (c.8, MeH); MS (ESI +, m/z): 83 [(M+Na) +, 00%], and [(M+H) +, %]; Anal. Calcd. (%) for C H 7 : C, 0.77; H,.. Found: C, 0.7; H,.. Methyl --crotonylquinate (c). R f (EtAc): 0.7; IR (NaCl): υ 3, 30, 3383,, 0, 8, 73, 77,, 3,,, 3, 0, and 08 cm - ; H NMR (acetone-d, 300 MHz): δ.87 (dd, 3H, H, 3 J HH., J HH.7 Hz),. (dd, H, H a, J HH 3., 3 J HH 0.0 Hz),.0-.3 (m, 3H, H +H e ), 3.70 (s, 3H, Me),. (d, H, H 3, J HH. Hz),.-.33 (m, H, H 3 +H ),. (d, H, H, 3 J HH. Hz),.7 (dd, H, H, 3 J HH 8., 3.0 Hz),.0 (s, H, H),.88 (dc, H, H 0, 3 J HH., J HH.7 Hz), and.7 (dc, H, H, 3 J HH.,. Hz); 3 C NMR (acetone-d, 7. MHz):ÀÃδ 8. (C ), 3.0 (C ), 3. (C ), 3. (Me),. (C ),. (C 3 ), 7. (C ), 0 7. (C ),. (C 0 ),. (C ), 7.0 (C ), and 7. (C 7 ); [α ] D = - (c., MeH); MS (EI +, m/z): 88 (M + -MeCH=CHC H, 7%), 70 (), (3), 00 (8), and (00); HRMS (m/z) Calcd. for C 8 H : Found: Anal. Calcd. (%) for C H 8 7 : C,.; H,.. Found: C,.; H,.. Methyl --benzoylquinate (d). R f (EtAc): 0.33; mp: 8- C; IR (NaCl): υ 3, 30, 30,, 3, 73,, 8,, 8, 38, 0, and 070 cm - ; H NMR (acetone-d, 300 MHz): δ.-.7 (m, H, H +H ), 3.7 (s, 3H, Me),.0-.8 (m, 3H, H 3 +H +H),. (d, H, H, 3 J HH. Hz),. (dd, H, H, 3 J HH 8.,.8 Hz),.08 (s, H, H), 7. (dd, H, H, 3 J HH 7.3 Hz), 7.3 (d, H, H 3, 3 J HH 7. Hz), and 8.0 (d, H, H, 3 J HH 7.3 Hz); 3 C NMR (acetone-d, 7. MHz): δ 3. (C ), 3.3 (C ), 3. (Me),.7 (C ),. (C 3 ), 7. (C ), 80. (C ),.8 (C ), 0 3. (C ), 3.3 (C 0 ), 3. (C 3 ), 7. (C ), and 7.3 (C 7 ); [α ] D = - (c 0.8, acetone); MS (ESI +, m/z): 3 [(M+H) +, 00%], and 33 [(M+Na) +, 8%]; Anal. Calcd. (%) for C H 8 7 : C, 8.0; H,.8. Found: C, 8.; H,.8. Methyl --hydrocinnamoylquinate (a). R f (EtAc): 0.3; mp: -3 C; IR (NaCl): υ 3, 8,, 87, 73, 7,, 3,, 30, and 080 cm - ; H NMR (acetone-d, 300 MHz): δ.3 (dd, H, H a, J HH 3., 3 J HH 0.0 Hz), (m, 3H, H +H e ),.8 (t, H, H 0, 3 J HH 7.7 Hz),. (t, H, H, 3 J HH 7.7 Hz), 3.70 (s, 3H, Me),.3 (d, H, H 3, J HH.8 Hz),.-.8 (m, H, H 3 +H ),.3 (d, H, H, 3 J HH.8 Hz),.70 (dd, H, H, 3 J HH 8., 3.0 Hz),.00 (s, H, H), and (m, H, H 3 +H +H ); 3 C NMR (acetone-d, 7. MHz): δ 3. (C ), 37. (C 0 ), 38. (C ), 3.0 (C ), 3. (Me),. (C ),. (C 3 ), 7.8 (C ), 7. (C ), 7. (C ),.8,.8 (C 3 +C ),. (C), 73. (C ), and 7.3 (C 7 ); 0 [α ] D = -0 (c.3, acetone); MS (EI +, m/z): 338 (M +, %), 30 (), 7 (7), 3 (), 33 (0), 0 S7

8 (00), and 77 (8); HRMS (m/z) Calcd. for C 7 H 7 : Found: Anal. Calcd. (%) for C 7 H 7 : C, 0.3; H,.. Found: C, 0.; H,.. Methyl --[3-(-hydroxyphenyl)propionyl]quinate (b). R f (EtAc): 0.; IR (NaCl): υ 338,, 3, 733,,, 30, 0, 30, 080, and 03 cm - ; H NMR (acetone-d, 300 MHz): δ.3 (dd, H, H a, J HH 3., 3 J HH 0. Hz), (m, 3H, H +H e ),. (t, H, H 0, 3 J HH 7.7 Hz),.8 (t, H, H, 3 J HH 7.7 Hz), 3. (s, 3H, Me),.-.7 (m, H, H 3 +H),. (dd, H, H, 3 J HH.,.8 Hz),.7 (d, H, H, 3 J HH 8. Hz), and 7.08 (d, H, H 3, 3 J HH 8.3 Hz); 3 C NMR (acetone-d, 7. MHz): δ 3.3 (C ), 37. (C 0 ), 38. (C ), 3.0 (C ), 3. (Me),. (C ),. (C 3 ), 7.8 (C ), 7. (C ),. (C ), 30.7 (C 3 ), 33. (C ), 7. (C ), 73.7 (C ), 0 and 7.3 (C 7 ); [α ] D = -37 (c.7, MeH); MS (ESI +, m/z): 3 [(M+H) +, 00%], 377 [(M+Na) +, 7%], and 33 [(M+K) + ]; Anal. Calcd. (%) for C 7 H 8 : C, 7.; H,.. Found: C, 7.; H,.3. Methyl --cinnamoylquinate (a). R f (EtAc): 0.3; mp: - C; IR (KBr): υ 3,, 30, 88, 73, 7, 3, 78,, 8, 0,, 07, and 00 cm - ; H NMR (acetone-d, 300 MHz): δ.7 (dd, H, H a, J HH 3., 3 J HH 0. Hz), (m, 3H, H +H e ), 3.7 (s, 3H, Me), (m, 3H, H 3 +H +H),. (d, H, H, 3 J HH.8 Hz),.8 (dd, H, H, 3 J HH.0, 3.0 Hz),.0 (s, H, H),.7 (d, H, H 0, 3 J HH Hz), (m, 3H, H +H), and (m, 3H, H +H 3 ); 3 C NMR (acetone-d, 7. MHz): δ 3. (C ), 3.3 (C ), 3. (Me),. (C ),. (C 3 ), 77.0 (C ), 7. (C ), 0. (C 0 ),. (C 3 ), 30. (C ), 3.8 (C ), 0 3. (C ),.8 (C ), 7. (C ), and 7. (C 7 ); [α ] D = - (c 0.7, acetone); MS (ESI +, m/z): 337 [(M+H) +, 00%], and 3 [(M+Na) +, %]; Anal. Calcd. (%) for C 7 H 0 7 : C, 0.7; H,.. Found: C, 0.7; H,.. Methyl --(-fluorocinnamoyl)quinate (b). R f (EtAc): 0.3; mp: -3 C; IR (KBr): υ 33, 3073, 8, 0, 73, 78, 38, 0,, 8, 3, 0, 7,, 088, and 08 cm - ; H NMR (acetone-d, 300 MHz): δ.8 (dd, H, H a, J HH 3., 3 J HH 0. Hz),.0-. (m, 3H, H +H e ), 3.7 (s, 3H, Me), (m, 3H, H 3 +H +H),.3 (bs, H, H),.8 (dd, H, H, 3 J HH 8.,.8 Hz),.07 (bs, H, H),.3 (d, H, H 0, 3 J HH Hz), 7. (dd, H, H, 3 J HH 8., 3 J HF 8. Hz), and (m, 3H, H +H 3 ); 3 C NMR (acetone-d, 7. MHz): δ 3.0 (C ), 3. (C ), 3. (Me),. (C ),. (C 3 ), 7. (C ), 7. (C ), 7. (d, C, C, J CF. Hz), 0.0 (C 0 ), 3. (d, C, C 3, 3 J CF 8.7 Hz), 3. (d, C, C, J CF. Hz),. (C ),.3 (d, C, C, 0 J CF 8.7 Hz), 7. (C ), and 7.3 (C 7 ); [α ] D = - (c.3, acetone); MS (ESI +, m/z): 3 [(M+H) +, 00%], 377 [(M+Na) +, 3%], and 33 S8

9 [(M+K) + ]; Anal. Calcd. (%) for C 7 H F 7 : C, 7.3; H,.; F,.3. Found: C, 7.7; H,.. S

10 Vinyl Coumarate (3b) 3 H 7 3b S0 H CDCl 3 8

11 Vinyl Coumarate (3b) 3 H 7 3b S 3 C CDCl 3 8

12 Vinyl Ferulate (3c) Me H 7 8 H CDCl c S

13 Vinyl Ferulate (3c) Me 3 H 7 8 3c (ppm) S3 3 C CDCl 3 0

14 Vinyl Hydrocinnamate (a) a H CDCl 3 S

15 Vinyl Hydrocinnamate (a) 3 7 a S 8 3 C CDCl 3

16 Vinyl 3-(-Hydroxyphenyl)propionate (b) 3 8 H 7 b H CDCl 3 S

17 Vinyl 3-(-Hydroxyphenyl)propionate (b) 3 8 H 7 b S7 3 C CDCl 3

18 Methyl --Cinnamoylshikimate (a) H CDCl C Me H 0 3 H 3 a S8

19 Methyl --Cinnamoylshikimate (a) 7 8 C Me H 0 3 H 3 a S 3 C CDCl 3

20 H C Me 3 H 7a Methyl --Hydrocinnamoylshikimate (7a) S0 H CDCl 3

21 Methyl --Hydrocinnamoylshikimate (7a) 7 8 C Me H 0 3 H 3 7a S 3 C CDCl 3

22 Cinnamic Anhydride (8a) 3 7 8a S H CDCl 3

23 Cinnamic Anhydride (8a) 3 7 8a S3 3 C CDCl 3

24 --Acetylcoumaric Anhydride (8b) H CDCl b 3 S

25 --Acetylcoumaric Anhydride (8b) b S 3 C CDCl 3

26 --Acetylferulic Anhydride (8c) 0 Me c H CDCl 3 S

27 --Acetylferulic Anhydride (8c) 0 Me c S7 3 C CDCl 3

28 -Metoxycinnamic Anhydride (8d) 8 Me 3 7 8d H CDCl 3 S8

29 -Metoxycinnamic Anhydride (8d) 8 Me 3 7 8d S 3 C CDCl 3

30 -Fluorocinnamic Anhydride (8e) H CDCl 3 F 7 8e 3 S30

31 -Fluorocinnamic Anhydride (8e) 3 F 7 8e S3 3 C CDCl 3

32 -Acetoxycinnamic Anhydride (a) a H CDCl 3 S3

33 -Acetoxycinnamic Anhydride (a) a S33 3 C CDCl 3

34 -Metoxycinnamic Anhydride (b) Me 0 b H CDCl 3 S3

35 -Metoxycinnamic Anhydride (b) Me S3 3 C CDCl 3 0 b

36 H 0 3 F 7 8 C Me 3 H 0e Methyl --(-Fluorocinnamoyl)shikimate (0e) S3 H CDCl 3

37 Methyl --(-Fluorocinnamoyl)shikimate (0e) 7 8 C Me H 0 3 H 3 F 0e S37 3 C CDCl 3

38 Methyl --Acetylquinate (a) 8 7 Me C H H 3 H 0 a H Acetone-d S38

39 Methyl --Acetylquinate (a) 8 7 Me C H H 3 H 0 a S3 3 C Acetone-d

40 Methyl --Acryloylquinate (b) 8 7 Me C H H H 3 0 H H 0 H b H Acetone-d S0

41 Methyl --Acryloylquinate (b) 8 7 Me C H H H 3 0 H H 0 H b S 3 C Acetone-d

42 Methyl --Crotonylquinate (c) 8 7 Me C H H H 3 0 H 0 H c S H Acetone-d

43 Methyl --Crotonylquinate (c) 8 7 Me C H H H 3 0 H 0 H c S3 3 C Acetone-d

44 8 7 Me C H d H H Methyl --Benzoylquinate (d) S H Acetone-d

45 Methyl --Benzoylquinate (d) 8 7 Me C H H 3 0 H 3 d S 3 C Acetone-d

46 Methyl --Hydrocinnamoylquinate (a) H Acetone-d 8 7 Me C H H 0 3 H 3 a S

47 Methyl --Hydrocinnamoylquinate (a) 8 7 Me C H H 0 3 H 3 a S7 3 C Acetone-d

48 Methyl --[3-(-Hydroxyphenyl)propionyl)]quinate (b) 8 7 Me C H H 0 3 H 3 H b S8 H Acetone-d

49 Methyl --[3-(-Hydroxyphenyl)propionyl]quinate (b) 8 7 Me C H H 0 3 H 3 H b S 3 C Acetone-d

50 8 7 Me C H 0 3 a Methyl --Cinnamoylquinate (a) H 3 H S0 H Acetone-d

51 Methyl --Cinnamoylquinate (a) 8 7 Me C H H 0 3 H 3 a S 3 C Acetone-d

52 Methyl --(-Fluorocinnamoyl)quinate (b) 8 7 Me C H H 0 3 H 3 F b S H Acetone-d

53 8 7 Me C H F b H H Methyl --(-Fluorocinnamoyl)quinate (b) S3 3 C Acetone-d