(1S,2S) 1-phenylpropane-1,2-diol, (1S,2S)-PPD

Biotransformations on larger scale are mostly limited to cases in which alternative chemical routes lack sufficient chemo-, regio-, or stereoselectivity. Here, we expand the applicability of biocatalysis by combining cheap whole cell catalysts with a microaqueous solvent system. Compared to aqueous systems, this permits manifoldly higher concentrations of hydrophobic substrates while maintaining stereoselectivity. We apply these methods to four different two-step reactions of carboligation and oxidoreduction to obtain 1-phenylpropane-1,2-diol (PPD), a versatile building block for pharmaceuticals, starting from inexpensive aldehyde substrates. By a modular combination of two carboligases and two alcohol dehydrogenases, all four stereoisomers of PPD can be produced in a flexible way. After thorough optimization of each two-step reaction, the resulting processes enabled up to 63 g L–1 product concentration (98% yield), space-time-yields up to 144 g L–1 d–1, and a target isomer content of at least 95%. Despite the use of whole cell catalysts, we did not observe any side product formation of note. In addition, we prove that, by using 1,5-pentandiol as a smart cosubstrate, a very advantageous cofactor regeneration system could be applied.

Stereoselective Two-Step Biocatalysis in Organic Solvent: Toward All Stereoisomers of a 1,2-Diol at High Product Concentrations

Jochen Wachtmeister†, Andre Jakoblinnert‡, and Dörte Rother*†

† IBG-1: Biotechnology, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany

‡ Piramal Healthcare UK Ltd., Division of Biocatalysis, The Wilton Centre, R345, TS10 4RF Redcar, United Kingdom

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.6b00232

Publication Date (Web): September 19, 2016

Copyright © 2016 American Chemical Society

*E-mail: Do.Rother@fz-juelich.de.

http://pubs.acs.org/doi/full/10.1021/acs.oprd.6b00232

(1S,3′S,4′S,5′S,6′R)-3′,4′,5′,6′-tetrahydro-6,6′-bis(hydroxymethyl)-spiro[2-benzofuran-1(3H),2-[2H]pyran]-3′,4′,5′-triol

(1S,3′S,4′S,5′S,6′R)-3′,4′,5′,6′-tetrahydro-6,6′-bis(hydroxymethyl)-spiro[2-benzofuran-1(3H),2-[2H]pyran]-3′,4′,5′-triol (15)

15 (663 g, 60% from 3) as a white crystal; 

mp 193–194 °C; [α]D25 +43.8° (c 1.07, H2O); 

1H NMR (400 MHz, CD3OD) δ: 3.46–3.49 (1H, m), 3.63–3.69 (1H, m), 3.75–3.85 (4H, m), 4.64 (2H, s), 5.10 (1H, d, J = 12.5 Hz), 5.15 (1H, d, J = 12.5 Hz), 7.23–7.27 (1H, m), 7.30–7.37 (2H, m); 

13C NMR (100 MHz, CD3OD) δ: 62.8, 65.0, 71.9, 73.5, 74.9, 76.2, 76.3, 111.6, 121.8, 121.9, 129.2, 140.2, 141.2, 142.5; 

MS (ESI) m/z: 299 [M + H]+; HRMS (ESI) calcd for C14H19O7 [M + H]+299.1125, found 299.1119.

J. Org. Chem., 2016, 81 (5), pp 2148–2153

DOI: 10.1021/acs.joc.5b02734

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KHAJURAHO, MADHYA PRADESH, INDIA

Khajuraho Group of Monuments

The Khajuraho Group of Monuments is a group of Hindu and Jain temples in Madhya Pradesh, India, about 175 kilometres southeast of Jhansi. They are one of the UNESCO World Heritage Sites in India.Wikipedia

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(1S,6R)-9-Oxa-3-azabicyclo[4.2.1]nonane

                       

9-Oxa-3-azabicyclo[4.2.1]nonane

9-Oxa-3-azabicyclo[4.2.1]nonane;  CAS 69928-94-5;
Molecular Formula:	C7H13NO
Molecular Weight:	127.18422 g/mol

(1R,3r,5S)-2′-((S)-1-Phenylethyl)-8-oxaspiro[bicyclo[3.2.1]octane-3,3′-[1,2]oxaziridine] (13)

(13) as a light orange oil. ¹H NMR (300 MHz, CDCl₃) δ 7.48–7.40 (m, 2H), 7.39–7.27 (m, 3H), 4.44–4.35 (m, 1H), 4.33–4.24 (m, 1H), 3.48 (q, J = 6.3 Hz, 1H), 2.33 (ddd, J = 12.9, 4.5, 3.5 Hz, 2H), 1.89 (d, J = 14.8 Hz, 1H), 1.71–1.60 (m, 1H), 1.55 (t, J = 4.2 Hz, 3H), 1.54–1.47 (m, 1H), 1.42–1.29 (m, 2H), 0.32 (ddd, J = 11.1, 6.9, 3.4 Hz, 1H) ppm. ¹³C NMR (75 MHz, CDCl₃) δ 141.0, 128.8, 128.1, 127.1, 82.0, 73.9, 73.3, 63.3, 43.0, 27.7, 27.6, 24.4 ppm.

(1S,6R)-3-((S)-1-Phenylethyl)-9-oxa-3-azabicyclo[4.2.1]nonan-4-one (14)

¹H NMR (300 MHz, CDCl₃) δ 7.29 (dddd, J = 15.5, 7.3, 5.0, 1.2 Hz, 5H), 6.18–6.04 (m, 1H), 4.38 (tt, J = 9.0, 7.7 Hz, 2H), 3.14 (d, J = 15.7 Hz, 1H), 2.92–2.75 (m, 3H), 2.11–1.82 (m, 4H), 1.50 (d, J= 7.1 Hz, 3H) ppm. ¹³C NMR (75 MHz, CDCl₃) δ 173.59, 140.25, 128.53, 127.37, 127.21, 75.61, 72.25, 51.03, 50.50, 50.44, 47.88, 28.75, 26.44, 16.01 ppm. [α]^21.8_D = 160.2° (c = 1, 100 mg/10 mL of MeOH).

(1S,6R)-3-((S)-1-Phenylethyl)-9-oxa-3-azabicyclo[4.2.1]nonane (15)

15 as a colorless oil. ¹H NMR (300 MHz, CDCl₃) δ 7.44–7.24 (m, 5H), 4.45 (t, J = 8.4 Hz, 1H), 4.38–4.28 (m, 1H), 3.85–3.74 (m, 1H), 2.77 (ddd, J = 19.5, 8.8, 4.1 Hz, 1H), 2.58 (dd, J = 10.6, 3.4 Hz, 2H), 2.43–2.28 (m, 1H), 2.23–2.06 (m, 1H), 2.02–1.84 (m, 4H), 1.44–1.29 (m, 4H) ppm. [α]^19.2_D = 25.683 (c = 0.989, 98.9 mg in 10 mL of MeOH).

(1S,6R)-9-Oxa-3-azabicyclo[4.2.1]nonane 11 as a white solid. ¹H NMR (300 MHz, CDCl₃) δ 9.88 (s, 1H), 9.34 (s, 1H), 4.71–4.31 (m, 2H), 3.56–2.88 (m, 4H), 2.49–1.70 (m, 6H) ppm.

ESI-MS found 128.0 (M + 1 ⁺. [α]^22.0_D = −10.88 (c = 0.92, 92 mg in 10 mL of MeOH).

OLD SYNTHESIS

1H NMR predict

(1S,6R)-9-Oxa-3-azabicyclo[4.2.1]nonane

EXPT  ¹H NMR (300 MHz, CDCl₃) δ 9.88 (s, 1H), 9.34 (s, 1H), 4.71–4.31 (m, 2H), 3.56–2.88 (m, 4H), 2.49–1.70 (m, 6H) ppm.

13C NMR PREDICT

REFERENCES

http://onlinelibrary.wiley.com/doi/10.1002/ardp.19923250205/abstract;jsessionid=61D5B2D4DA952E04EF91805DA6314857.f03t02

http://pubs.acs.org/doi/full/10.1021/acs.oprd.6b00213

//////////////////Chiral Bicyclic Lactam

C1CC2CCNCC1O2

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(1S,6R)-9-Oxa-3-azabicyclo[4.2.1]nonane

                       

9-Oxa-3-azabicyclo[4.2.1]nonane

9-Oxa-3-azabicyclo[4.2.1]nonane;  CAS 69928-94-5;
Molecular Formula:	C7H13NO
Molecular Weight:	127.18422 g/mol

(1R,3r,5S)-2′-((S)-1-Phenylethyl)-8-oxaspiro[bicyclo[3.2.1]octane-3,3′-[1,2]oxaziridine] (13)

(13) as a light orange oil. ¹H NMR (300 MHz, CDCl₃) δ 7.48–7.40 (m, 2H), 7.39–7.27 (m, 3H), 4.44–4.35 (m, 1H), 4.33–4.24 (m, 1H), 3.48 (q, J = 6.3 Hz, 1H), 2.33 (ddd, J = 12.9, 4.5, 3.5 Hz, 2H), 1.89 (d, J = 14.8 Hz, 1H), 1.71–1.60 (m, 1H), 1.55 (t, J = 4.2 Hz, 3H), 1.54–1.47 (m, 1H), 1.42–1.29 (m, 2H), 0.32 (ddd, J = 11.1, 6.9, 3.4 Hz, 1H) ppm. ¹³C NMR (75 MHz, CDCl₃) δ 141.0, 128.8, 128.1, 127.1, 82.0, 73.9, 73.3, 63.3, 43.0, 27.7, 27.6, 24.4 ppm.

(1S,6R)-3-((S)-1-Phenylethyl)-9-oxa-3-azabicyclo[4.2.1]nonan-4-one (14)

¹H NMR (300 MHz, CDCl₃) δ 7.29 (dddd, J = 15.5, 7.3, 5.0, 1.2 Hz, 5H), 6.18–6.04 (m, 1H), 4.38 (tt, J = 9.0, 7.7 Hz, 2H), 3.14 (d, J = 15.7 Hz, 1H), 2.92–2.75 (m, 3H), 2.11–1.82 (m, 4H), 1.50 (d, J= 7.1 Hz, 3H) ppm. ¹³C NMR (75 MHz, CDCl₃) δ 173.59, 140.25, 128.53, 127.37, 127.21, 75.61, 72.25, 51.03, 50.50, 50.44, 47.88, 28.75, 26.44, 16.01 ppm. [α]^21.8_D = 160.2° (c = 1, 100 mg/10 mL of MeOH).

(1S,6R)-3-((S)-1-Phenylethyl)-9-oxa-3-azabicyclo[4.2.1]nonane (15)

15 as a colorless oil. ¹H NMR (300 MHz, CDCl₃) δ 7.44–7.24 (m, 5H), 4.45 (t, J = 8.4 Hz, 1H), 4.38–4.28 (m, 1H), 3.85–3.74 (m, 1H), 2.77 (ddd, J = 19.5, 8.8, 4.1 Hz, 1H), 2.58 (dd, J = 10.6, 3.4 Hz, 2H), 2.43–2.28 (m, 1H), 2.23–2.06 (m, 1H), 2.02–1.84 (m, 4H), 1.44–1.29 (m, 4H) ppm. [α]^19.2_D = 25.683 (c = 0.989, 98.9 mg in 10 mL of MeOH).

(1S,6R)-9-Oxa-3-azabicyclo[4.2.1]nonane 11 as a white solid. ¹H NMR (300 MHz, CDCl₃) δ 9.88 (s, 1H), 9.34 (s, 1H), 4.71–4.31 (m, 2H), 3.56–2.88 (m, 4H), 2.49–1.70 (m, 6H) ppm.

ESI-MS found 128.0 (M + 1 ⁺. [α]^22.0_D = −10.88 (c = 0.92, 92 mg in 10 mL of MeOH).

OLD SYNTHESIS

1H NMR predict

(1S,6R)-9-Oxa-3-azabicyclo[4.2.1]nonane

EXPT  ¹H NMR (300 MHz, CDCl₃) δ 9.88 (s, 1H), 9.34 (s, 1H), 4.71–4.31 (m, 2H), 3.56–2.88 (m, 4H), 2.49–1.70 (m, 6H) ppm.

13C NMR PREDICT

REFERENCES

http://onlinelibrary.wiley.com/doi/10.1002/ardp.19923250205/abstract;jsessionid=61D5B2D4DA952E04EF91805DA6314857.f03t02

http://pubs.acs.org/doi/full/10.1021/acs.oprd.6b00213

//////////////////Chiral Bicyclic Lactam

C1CC2CCNCC1O2

 Pakistan,  Sindh, 

Tharparkar District

Tharparkar District

Tharparkar District, is one of the twenty nine districts of Sindh province in Pakistan. It is headquartered at Mithi. It has the lowest Human Development Index of all the districts in Sindh. Wikipedia

Latitude and Longitude on Globe is 24.20.54.42N 70.43.05.87E

2nd Highest peak of Karoonjhar about 1067 ft Altitude.. Latitude and Longitude on Globe is 24.19.45.20N 70.43.19.69E

Highest peak of Karoonjhar 

Kakbanglow Rd near Mirpur Khas Sindh

Main gate of Mir Mehboob Ali Talpur (MPA) Mir Landhi Sindh

 

Main outer entrance of Mir Landhi village for residential area

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