university of groningen enzymatic preparation of optically

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University of Groningen Enzymatic preparation of optically active carboxylic acid derivatives using ochrobactrum anthropi de Vries, Erik Jan IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 1997 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): de Vries, E. J. (1997). Enzymatic preparation of optically active carboxylic acid derivatives using ochrobactrum anthropi. s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne- amendment. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 01-10-2021

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Page 1: University of Groningen Enzymatic preparation of optically

University of Groningen

Enzymatic preparation of optically active carboxylic acid derivatives using ochrobactrumanthropide Vries, Erik Jan

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.

Document VersionPublisher's PDF, also known as Version of record

Publication date:1997

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):de Vries, E. J. (1997). Enzymatic preparation of optically active carboxylic acid derivatives usingochrobactrum anthropi. s.n.

CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).

The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.

Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.

Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.

Download date: 01-10-2021

Page 2: University of Groningen Enzymatic preparation of optically

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Page 8: University of Groningen Enzymatic preparation of optically

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Contents

Voorwoord � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 9

Contents � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 9,,

Chapter OneIntroduction

��� )URP HYHU\GD\ OLIH WR PLFUR RUJDQLVPV WR RUJDQLF FKHPLVWU\

DQG EDFN DJDLQ � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �

����� (Q]\PHV LQ ,QGXVWU\ � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �

����� &KLUDOLW\ DQG WKH 3KDUPDFHXWLFDO ,QGXVWU\ � � � � � � � � � � � � � � � � � � � � �

����� 7KH '60 SURFHVV IRU DPLQR DFLGV � � � � � � � � � � � � � � � � � � � � � � � � � � � � �

����� 0\FREDFWHULXP QHRDXUXP � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �

����� $ VKRUW FRXUVH RQ PLFURELRORJ\� FODVVLILFDWLRQ RI PLFUR RUJDQLVPV � �

����� 3UREOHPV ZLWK FODVVLILFDWLRQ � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �

����� ,VRODWLRQ RI D QHZ DPLGH�K\GURO\]LQJ PLFUR RUJDQLVP � � � � � � � � � � � �

����� &ODVVLILFDWLRQ RI ��$� 2FKUREDFWUXP DQWKURSL � � � � � � � � � � � � � � � � � �

����� 6SHFLILFLW\ RI 2FKUREDFWUXP DQWKURSL � � � � � � � � � � � � � � � � � � � � � � � � �

��� 2FKUREDFWUXP DQWKURSL YHUVXV 3V� SXWLGD DQG 0� QHRDXUXP � � � � � ��

��� 3DUDOOHO UHVHDUFK DW '60 /DERUDWRULHV � � � � � � � � � � � � � � � � � � � � � � � ��

��� 7KH IUDPHZRUN ZLWKLQ ZKLFK WKH UHVHDUFK KDV EHHQ SHUIRUPHG�

7KH ,23 &DWDO\VLV 3URJUDPPH � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

��� $LP RI WKLV WKHVLV � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

��� 6XUYH\ RI WKLV WKHVLV � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

���� 5HIHUHQFHV � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

Chapter TwoMandelic acid derivatives

��� ,QWURGXFWLRQ � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

��� $SSOLFDWLRQ RI PDQGHOLF DFLGV LQ FKHPLVWU\ � � � � � � � � � � � � � � � � � � � ��

��� &KHPLFDO V\QWKHVLV RI RSWLFDOO\ DFWLYH PDQGHOLF DFLGV � � � � � � � � � � � ��

����� %LRFKHPLFDO URXWHV WR RSWLFDOO\ DFWLYH PDQGHOLF DFLGV � � � � � � � � � � � ��

����� $PLGDVH HQ]\PHV WKDW SURGXFH PDQGHOLF DFLGV � � � � � � � � � � � � � � � � ��

����� 6\QWKHVLV RI WKH K\GUR[\ DFLGV � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

����� +\GURJHQ F\DQLGH DGGLWLRQ WR D VXEVWLWXWHG DOGHK\GH � � � � � � � � � � � ��

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����� 6\QWKHVLV RI K\GUR[\ DFLGV IURP WKH VXEVWLWXWHG DFHWRSKHQRQHV � � � ��

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������ ([SHULPHQWDO VHFWLRQ� JHQHUDO V\QWKHWLF UHPDUNV � � � � � � � � � � � � � � � ��

������ *HQHUDO UHPDUNV RQ HQ]\PDWLF UHDFWLRQV � � � � � � � � � � � � � � � � � � � � � ��

���� $SSHQGL[� +3/& GDWD RI VHOHFWHG FRPSRXQGV � � � � � � � � � � � � � � � � � ��

���� 5HIHUHQFHV � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

Chapter Three2,2-dimethyl-[1,3]dioxolan-4-ones

��� *HQHUDO LQWURGXFWLRQ � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

����� ,QWURGXFWLRQ WR >���@GLR[RODQ���RQHV � � � � � � � � � � � � � � � � � � � � � � � � ��

����� 0HWKRGV RI SUHSDUDWLRQ RI ����GLPHWK\O�GLR[RODQRQHV � � � � � � � � � � ��

����� 5HDFWLYLW\ RI K\GUR[\ DFLGV ZLWK '03� VXEVWLWXHQW HIIHFW DQG

SURSHUWLHV RI WKH GLR[RODQRQHV � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

��� 7KH UHDFWLYLW\ RI WKH GLR[RODQRQHV UHYLHZHG� 5LQJ RSHQLQJ� DON\ODWL�

RQ� DGGLWLRQ� UHGXFWLRQ DQG RWKHU UHDFWLRQV � � � � � � � � � � � � � � � � � � � ��

��� 5HDFWLRQ RI GLR[RODQRQHV ZLWK DPPRQLD RU RWKHU DPLQHV� D QHJOHFWHG

URXWH WR �VXEVWLWXWHG� K\GUR[\ DPLGHV � � � � � � � � � � � � � � � � � � � � � � � ��

��� 5HDFWLRQ RI VRPH RWKHU GLR[RODQRQHV ZLWK DPPRQLD � � � � � � � � � � � � ��

��� 6XPPDU\ � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

��� ([SHULPHQWDO � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

��� 5HIHUHQFHV � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

Chapter FourExploring the scope of substrates

��� ,QWURGXFWLRQ � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

��� (VWHUV RI DPLQR DFLGV � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

����� ,QWURGXFWLRQ RQ DPLGH FRQWDLQLQJ VXEVWUDWHV � � � � � � � � � � � � � � � � � � ��

����� $PLGHV KDYLQJ DON\O JURXSV LQWURGXFLQJ VWHULF EXON DW WKH α�SRVLWLRQ������� $PLGHV KDYLQJ SRODUL]DEOH JURXSV DW WKH α�SRVLWLRQ � � � � � � � � � � � � ��

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����� $PLGHV KDYLQJ K\GURJHQ ERQGLQJ IXQFWLRQDO JURXSV � � � � � � � � � � � ��

����� $QDORJXHV RI PDQGHODPLGH� GLIIHUHQW DURPDWLF ULQJV � � � � � � � � � � � ��

����� 6\QWKHVLV RI ��IXUDQ���\O���K\GUR[\�DFHWDPLGH � � � � � � � � � � � � � � � ��

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����� 7KH 3DVVHULQL WKUHH FRPSRQHQW UHDFWLRQ � � � � � � � � � � � � � � � � � � � � � � ��

����� $PLGH FRQWDLQLQJ VXEVWUDWHV RI YHU\ GLIIHUHQW VWUXFWXUH� K\GDQWRLQV��

����� 3URFKLUDO GLDPLGHV EDVHG RQ PDORQLF DFLG � � � � � � � � � � � � � � � � � � � � ��

����� 5HDVRQV IRU WKH ODFN RI K\GURO\VLV � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

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Chapter FiveTechnology

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��� ([SHULPHQWDO� PDWHULDOV DQG PHWKRGV � � � � � � � � � � � � � � � � � � � � � ���

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Summary � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ���

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1.10 References

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�� &� :HL]PDQQ� &KHP $EVWU�� ��� ����� 1919� %ULW� 3DW� 1R� ����� 0DUFK � �UG

1915�� %HHFKDP 5HVHDUFK /DERUDWRULHV� 6XVVH[� 1DWXUH� ���� ���� 1959�� &� *XHUULHU�7DNDGD� 6� $OWPDQ� 6FLHQFH� ���� ���� 1984�� $�-� =DXJ� 7�5� &HFK� 6FLHQFH� ���� ���� 1986�� 7�5 &HFK� *HQH� ���� ��� 1993�� 5� 5DZOV� &(1� ��� -DQXDU\ �� � ��� 1996WK

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/RQGRQ 1985��� /�/� :HL� :�-� *RX[� %LRRUJ� &KHP�� ��� ��� 1992� -�0� /DYDO� -� 0RLURX[�&�

%RXUGLOORQ� %LRWHFKQRO� %LRHQJLQ�� ��� ���� 1991��� :� *HUKDUW]� (Q]\PHV LQ ,QGXVWU\� &K� �� 9&+ 9HUODJ� :HLQKHLP� 1990��� .LUN�2WKPHU� (QF\FORSHGLD RI &KHPLFDO 7HFKQRORJ\� � (G�� :LOH\� 1HZ <RUN�WK

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*UHHQ� /RQGRQ� 1907� $�5� &XVKQ\� %LRORJLFDO UHODWLRQV RI RSWLFDOO\ LVRPHULF

VXEVWDQFHV� :LOOLDPV DQG :LONLQV� %DOWLPRUH� 1926��� 7KDOLGRPLGH� 'UXJ 5HV�� ��� ����� 1979� 3URIHQ 'UXJV� -� 3KDUP� 3KDUPDFRO�� ���

���� 1976� )XUWKHU H[DPSOHV� %� +ROPVWHG� &KLUDOLW\ DQG %LRORJLFDO $FWLYLW\� $ODQ

5� /LVV� ,QF�� 1HZ <RUN� 1990��� )RRG DQG 'UXJ $GPLQLVWUDWLRQ� &KLUDOLW\� �� ���� 1992��� -�6� 0LOOHUVKLS� $� )LW]SDWULFN� &KLUDOLW\� �� ���� 1993��� +�-� 5RWK� 3KDUPDFHXWLFDO &KHPLVWU\� (OOLV +RUZRRG� &KLFKHVWHU�9RO �� 1988��� %� .DSWHLQ� ,QWHUQDWLRQDO 3DWHQW� :2 ��������� �� -XQH 1995QG

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*�1� :RRGUXII� -� 0HG� &KHP�� ��� ���� 1991��� )� )RUPDJJLR� &� 7RQLROR� 0� &ULVPD� *� 9DOOH� +�(� 6FKRHPDNHU� -� .DPSKXLV� %�

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%DOWLPRUH� 1993��� %� +ROPHV� 0� 3RSRII� 0� .LUHGMLDQ� .� .HUVWHUV� ,QW� -� 6\VW� %DFWHULRO�� ��� ����

1988��� 7DWXP HW DO�� 0DQ� &OLQ� 0LFURELRO�� � (G�� $PHULFDQ 6RFLHW\ IRU 0LFURELRORJ\�QG

(�+� /HQHWWH (G�� 1974��� 7�-� &LHVODN� 0�/� 5REE� &�-� 'UDELFN� *�:� )LVFKHU� &OLQ� ,QIHFW� 'LV�� ��� ����

1992� &� %L]HW� -� %L]HW� 3DWKRO� %LRO�� ��� ���� 1995� ' $OQRU� 1� )ULPRGW�0ROOHU�

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&RPP�� ���� ���� 1989��� +� 0XUDVH� $� 6XJLKDUD� 7� 0XUR� <� 6KLPDGD� <� 7RPLQDJD� $JULF� %LRO� &KHP��

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4-Methoxy-phenyl-(trimethylsilyloxy)-acetonitrile

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Page 49: University of Groningen Enzymatic preparation of optically

3$� 53�+3/& FROXPQ ZLWK SHQLFLOODPLQH FRDWLQJ� $'� +3/& FROXPQ ZLWK DP\ORVH FRDWLQJ�[a]

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PJ RI VXOSKXULF DFLG DQG �� µO RI ZDWHU� 7KLV ELSKDVLF PL[WXUH ZDV VWLUUHG DQG KHDWHG

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2.11 Appendix: HPLC data of selected compounds

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Page 50: University of Groningen Enzymatic preparation of optically

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1. (�5� 3DUPHH� 2� 7HPSNLQ� 6� 0DVDPXQH� $� $ELNR� -� $P� &KHP� 6RF�� ���� �����

1991

�� FP $' ���� ���� +H[�L3$ ��� ��� �����������

��20H� �� FP 3$ �� ��� :DWHU�L3$ � ��� �����PDQGHOLF DFLG �����

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�� FP 3$ ���� ���� :DWHU�L3$ � ��� ����������

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2.12 References

Page 51: University of Groningen Enzymatic preparation of optically

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2. /� $UQDXG�6HELOORWWH� (� 6HJRW� &KHP� $EVWU�� ���� 3�����]� (3 �������� 1RY � �QG

19953. $� %UDLJ� 0� )UH\� $� .UDPHU� &KHP� $EVWU�� ���� 3������Y� '( ����������� -DQ

� � 1996WK

4. &� (FNKDUGW� +� :LOO� &KHP� $EVWU�� ���� 3������I� &+ �������� 'HF �� � 1986VW

5. )�$� $JULFROD� :�(� &RROH\� &KHP� $EVWU�� ���� 3������N� (3 �������� -XO\ � �VW

19886. +� 0RUL\DPD� +� 6KLPL]X� 0� ,WR� <� :DWDQDEH� &KHP� $EVWU�� ���� 3������Z�

-3 ����������� -XO\ � � 1986QG

7. 7� $LNDZD� &KHP� $EVWU�� ���� 3 �����I� -3 ����������� 2FW � � 1986WK

8. 7� .DPLPXUD� &KHP� $EVWU�� ���� 3�����Z� -3 ���������� )HE �� � 1988WK

9. +�+� .RSH� <�6� 7VDQWUL]RV� -�$� )RUWLQ� .�.� 2JLOYLH� &DQ� -� 0LFURELRO�� ��� ����

199110. (�-� 9DOHQWH� -� =XENRZVNL� '�6� (JJOHVWRQ� &KLUDOLW\� �� ���� 199211. (�-� 9DOHQWH� &�:� 0LOOHU� -� =XENRZVNL� '�6� (JJOHVWRQ� ;� 6KXL� &KLUDOLW\� �� ����

1995� $� &ROOHW� )� 9LJQH�0DHGHU� 1HZ -� &KHP�� ��� ���� 1995� 6� /DUVHQ� +�/RSH] GH 'LHJR� $&+�0RGHOV &KHP�� ���� ���� 1995� 7� 6KLUDLZD� 0� 1DNDPXUD�0� 1REHRND� +� .XURNDZD� %XOO� &KHP� 6RF� -SQ�� ��� ����� 1986� <� +RQGD�&KHP� $EVWU�� ���� 3������U� -3 ����������� )HE ��WK� ����� 5� +DVHJDZD�

&KHP� $EVWU�� ���� 3�����X� -3 ����������� 1RY �WK� 198412. +�&� %URZQ� *�*� 3DL� 3�.� -DGKDY� -� $P� &KHP� 6RF�� ���� ����� 198413. 6�3� %DNVKL� (�(� 7XUQHU� -� &KHP� 6RF�� ���� 196114. '�0� %RYH\� (�(� 7XUQHU� -� &KHP� 6RF�� ����� 195115. ,� 2MLPD� <� 0L\D]DZD� 0� .XPDJDL� -� &KHP� 6RF�� &KHP� &RPPXQ�� ���� 197616. -�'� 0RUULVRQ� +�6� 0RVKHU� $V\PPHWULF 2UJDQLF 5HDFWLRQV� &K� �� 3UHQWLFH +DOO

,QF�� 1HZ -HUVH\� 197117. 7� .RODVD� 0�-� 0LOOHU� -� 2UJ� &KHP�� ��� ����� 198718. 6��&�-� )X� 6�0� %LUQEDXP� -�3� *UHHQVWHLQ� -� $P� &KHP� 6RF�� ��� ����� 195419. <� 6DNDL� .� 6DWR� ,� ,WR� )� 7DNDKDVKL� %XOO� &KHP� 6RF� -SQ����� ���� 198920. $�,� 0H\HUV� -� 6ODGH� -� 2UJ� &KHP�� ��� ����� 198021. 8� *HUODFK� 7� +DXEHQUHLFK� 6� +XHQLJ� &KHP� %HU�� ���� ����� 199422. $� 0LVLHZLF]� .� 5DGZDQ� %� -DQXV]HZVND� 0HG\F\QD 3UDF\� ��� ���� 199123. )� *REED� )� &DYDOOHUL� '� %RQWDGL� 3� 7RUUL� 5� 'DLQHVH� 6FDQG� -� :RUN� (QYLURQ�

+HDOWK� ��� ���� 199524. &�$� )HZVRQ� )(06 0LFURELRO� /HWW�� ��� ��� 198825. A.Y. Tsou, S.C. Ransom, J.A. Gerlt, D.D. Buechter, P.C. Babbitt, G.L. Kenyon,

%LRFKHPLVWU\� ��� ����� 199026. '�3� %DNHU� &� .OHDQWKRXV� -�1� .HHQ� (� :HLQKROG� %LRFKHP� -�� ���� ���� 199227. *�$� 3HWVNR� *�/� .HQ\RQ� -�$� *HUOW� '� 5LQJH� :� .R]DULFK� 7,%6� ��� ���� 1993

Page 52: University of Groningen Enzymatic preparation of optically

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28. -� %RMDUVNL� -�2[HOEDUN� &� $QGHUVVRQ� 6� $OOHQPDUN� &KLUDOLW\� �� ���� 199329. -�$� /DQGUR� $�7� .DOODUDNDO� 6�&� 5DQVRP� -�$� *HUOW� -�:� .R]DULFK� '�-� 1HLGKDUW�

*�/� .HQ\RQ� %LRFKHPLVWU\� ��� ����� 199130. <� 3RFNHU� 1� 0DWDPRUL� %LRFKHPLVWU\� ��� ����� 197331. 5� &KHQHYHUW� 0� /HWRXUQHDX� &DQ� -� FKHP�� ��� ���� 199032. +�%� .DJDQ� -�&� )LDXG� 7RSLFV LQ 6WHUHRFKHPLVWU\� (�/� (OLHO DQG 6�+� :LOHQ (G·V�

:LOH\� 1HZ <RUN� ��� ���� 198833. :� 0DUFNZDOG� $� 0F.HQ]LH� %HU�� ��%� ����� 189934. +� Y�G� 'HHQ� $�'� &XLSHU� 5�3� +RI� $� Y� 2HYHUHQ� %�/� )HULQJD� 5�0� .HOORJJ�

-� $P� &KHP� 6RF�� ���� ����� 199635. ,�%� 8WNLQ� 0�0� <DNLPRY� /�1� 0DWYHHYD� (�,� .R]O\DN� ,�6� 5RJR]KLQ� =�*�

6RORPRQ� $�0� %H]ERURGRY� )(06 0LFURELRO� /HWW�� ��� ���� 199136. 7� 6HPELULQJ� -� :LQWHU� $SSO� 0LFURELRO� %LRWHFK�� ��� ��� 198937. *� 6X]XNL� &KHP� $EVWU�� ���� 3�����Q� -3 ����������� -XQH �� � 1986WK

38. '�-� 9DVLF�5DFNL� 0� -RQDV� &� :DQGUH\� :� +XPPHO� 0��5� .XOD� $SSO�

0LFURELRO� %LRWHFK�� ��� ���� 198939. <� <DPD]DNL� +� 0DHGD� &KHP� $EVWU�� ���� 3�����\� -3 ��������� -XO\ �� �WK

198640. '�/� 9DQGHU -DJW� (� 'DXE� -�$� .URKQ� /��3�%� +DQ� %LRFKHPLVWU\� ��� ����� 197541. 7� (QGR� .� 7DPXUD� &KHP� $EVWU�� ���� 3������D� (3 �������� )HE �� � 1993WK

42. )� (IIHQEHUJHU� 7� =LHJOHU� 6� )RHUVWHU� $QJHZ� &KHP�� ��� ���� 1987� )�(IIHQEHUJHU� %� +RHUVFK� 6� )RHUVWHU� 7� =LHJOHU� 7HWUDKHGURQ /HWW�� ��� �����

1990� )� (IIHQEHUJHU� %� *XWWHUHU� 7� =LHJOHU� (� (FNKDUGW� 5� $LFKKRO]� /LHELJV$QQ� &KHP�� �� ��� 1991� (� 6PLWVNDPS�:LOPV� -� %UXVVHH� $� Y�G *HQ� *�-�0� YDQ6FKDUUHQEXUJ� -�%� 6ORRWKDDN� 5HFO� 7UDY� &KLP�� 3D\V�%DV� ���� ���� 1991� 3�=DQGEHUJHQ� -� Y�G /LQGHQ� -� %UXVVHH� $� Y�G *HQ� 6\QWK� &RPPXQ�� ��� �����

1991� -� %UXVVHH� (�&� 5RRV� $� Y�G *HQ� 7HWUDKHGURQ /HWW�� ��� ����� 1988

43. +� 0RRUODJ� &KLUDO α�VXEVWLWXWHG α�K\GUR[\ DFLGV� 3K�'� WKHVLV� 8QLYHUVLW\ RI*URQLQJHQ� 1991

44. )� ,VKLPXUD� 6� ,VKLNDZD� 6� $NL\DPD� 0� 7DNDGD� &KHP� $EVWU�� ���� 3�����Y�

-3 ��������� )HE �� � 1990QG

45. 7� 0L\D]DZD� 6� .XULWD� 6� 8HML� 7� <DPDGD� 6� .XZDWD� -� &KHP� 6RF�� 3HUNLQ ��

����� 199246. +�6� %HYLQDNDWWL� $�$� %DQHUML� 5�9� 1HZDGNDU� -� 2UJ� &KHP�� ��� ����� 198947. $�0� .OLEDQRY� &KHPWHFK� ���� 198648. .� 6DNDPRWR� 1� )XMLPRWR� 7� 0RULNDZD� &KHP� $EVWU�� ���� 3������V� -3

���������� 0D\ � � 1986WK

49. .� 6DNDVKLWD� 7� 1DNDPXUD� ,� :DWDQDEH� &KHP� $EVWU�� ���� 3������M� -3

���������� 6HSW � � 1985WK

50. :�-�-� YDQ GHQ 7ZHHO� 7�-�*�0� YDQ 'RRUHQ� 3�+� GH -RQJH� %� .DSWHLQ� $�/�/�

Page 53: University of Groningen Enzymatic preparation of optically

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'XFKDWHDX� -� .DPSKXLV� $SSO� 0LFURELRO� %LRWHFKQRO�� ��� ���� 199351. *�/� *UXQHZDOG� :�-� %URXLOOHWWH� -�$� )LQQH\� 7HWUDKHGURQ /HWW�� ��� ����� 198052. )� 'XERXGLQ� 3K� &D]HDX� )� 0RXOLQHV� 2 /DSRUWH� 6\QWKHVLV� ���� 198253. -�6� %XFN� -� $P� &KHP� 6RF�� ��� ����� 193354. 6� &]DSOLFNL� 6W� Y� .RVWDQHFNL� 9� /DPSH� %HU�� ��� ���� 190955. 6� &DFFKL� '� 0LVWL� /� /D 7RUUH� 6\QWKHVLV� ���� 198056. -�6� %XFN� :�6� ,GH� 2UJ� 6\QWK� &ROO� 9RO�� �� ��� 194357. -� -DPPRW� 5� 3DVFDO� $� &RPPH\UDV� 7HWUDKHGURQ /HWW�� ��� ���� 198958. .�7� /LX� 0�+� 6KLK� +�:� +XDQJ� &�-� +X� 6\QWKHVLV� ���� 198859. )� %HFNH� +� )OHLJ� 3� 3l�OHU� /LHELJV $QQ� &KHP������ ���� 197160. $�5� .DWULW]N\� %� 3LODUVNL� /� 8URJGL� 6\QWKHVLV� ���� 198961. $� 3LQQHU� )U� .OHLQ� %HU�� ��� ����� 187762. (�1� =LO·EHUPDQ� 5XVV� &KHP� 5HY�� ��� ���� 196263. -�-� .OLQJHQEHUJ� 2UJ� 6\QWK�� &ROO� 9RO� ,9� ���� 196364. $� %DQG\RSDGK\D\� 8�%� %DJFKL� *� 3RGGHU� 6�.� 0RLWUD� -� ,QGLDQ &KHP� 6RF�� ���

���� 198965. $� 0HU]� 6\QWKHVLV� ���� 197466. &�+� =KRX� '�4� <XDQ� 5�*� ;LH� 6\QWK� &RPPXQ�� ��� ��� 199467. '� 6DOYDWLHUUD� &� -DLPH� $� 9LUJLOL� )� 6DQFKH]�)HUUDQGR� -� 2UJ� &KHP�� ��� �����

1996; .� 7DNDKDVKL� <� 2KWVXND� 6� 1DNDGD� .� +DWWRUL� -� ,QFO� 3KHQ� 0RO� 5HFRJ�&KHP�� ��� ��� 1991

68. .� 0DWVXPRWR� 6� +DVKLPRWR� 7� 8FKLGD� 7� 2NDPRWR� 6� 2WDQL� &KHP� %HU�� ����

����� 198969. /�)� $XGULHWK� -� .OHLQEHUJ� -� 2UJ� &KHP�� �� ���� 193870. +� <D]DZD� .� 7DQDND� .� .DUL\RQH� 7HWUDKHGURQ /HWW�� ��� ����� 197471. 0�)� /LSWRQ� $� %DVKD� 6�0� :HLQUHE� 2UJDQLF 6\QWKHVLV� ��� ��� 1979� -�,� /HYLQ�

(� 7XURV� 6�0� :HLQUHE� 6\QWK� &RPPXQ�� ��� ���� 198272. 5� $QVFK�W]� 5� %|FKHU� $QQ�� ���� ��� 190973. *�(� 3KLOEURRN� -� 2UJ� &KHP�� ��� ���� 195474. &�6� &KHQ� <� )XMLPRWR� *� *LUGDXNDV� &�-� 6LK� -� $P� &KHP� 6RF�� ���� �����

198275. .� )DEHU� +� +|QLJ� $ IUHHZDUH SURJUDP IRU FDOFXODWLQJ DQG SORWWLQJ (�IDFWRUV

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�&'&O � δ ���� �&+ �� ���� �&+ �� ���� �&+�� ���� �&+ �� ����� �&+�� ����� �& ��� � � � T

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Hydantoins were prepared via the following standard procedure:

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Diethylmalonate was alkylated in the following standard way:

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2-Substituted diethylmalonates were aminated in the following standard way:

2-Pentyl malonamide 4.35e

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2-Carbamoyl-heptanoic acid (2-Pentyl-malonic acid mono amide) 4.40

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2,2-Dimethyl-5-pentyl-[1,3]dioxan-4,6-dione (Pentyl Meldrum’s acid) 4.42

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4.11 References

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�� <� $VDQR� $� 1DND]DZD� <� .DWR� .� .RQGR� -� %LRO� &KHP�� ���� ������ 1989� <�$VDQR� 7� 0RUL� 6� +DQDPRWR� <� .DWR� $� 1DND]DZD� %LRFKHP� %LRSK\V� 5HV�

&RPPXQ�� ���� ���� 1989�� %� +LUUOLQJHU� $� 6WRO]� +��-� .QDFNPXVV� -� %DFW�� ���� ����� 1996�� )�5� .LQGHU� 0�$� -DURVLQVNL� :�.� $QGHUVRQ� -� 2UJ� &KHP�� ��� ����� 1991�� :�-�-� YDQ GHQ 7ZHHO� 7�-�*�0� YDQ 'RRUHQ� 3�+� GH -RQJH� %� .DSWHLQ� $�/�/�

'XFKDWHDX� -� .DPSKXLV� $SSO� 0LFURELRO� %LRWHFKQRO�� ��� ���� 1993�� :�-� 0LGGOHWRQ� (�0� %LQJKDP� -� 2UJ� &KHP�� ��� ����� 1980�� *�+� 3RVQHU� &�(� :KLWWHQ� 3�(� 0F)DUODQG� -� $P� &KHP� 6RF�� ��� ����� 1972�� ,� 8JL� $QJHZ� &KHP�� ,QW� (G� (QJO�� �� �� 1962�� +�5� +HQ]H� /�0� /RQJ� -� $P� &KHP� 6RF�� ��� ����� 1941�� 0�-� *DUFLD� 5� $]HUDG� 7HWUDKHGURQ� $V\PP�� �� ��� 1997��� &� %DOO\� )� /HXWKDUGW� +HOY� &KLP� $FWD� ��� ���� 1970� &�-� )UDQFLV� -�%� -RQHV�

-� &KHP� 6RF�� &KHP� &RPPXQ�� ���� 1984� *�0�5� 7RPER� +�3� 6FKDU� ;�)HUQDQGHV� ,� %XVTXHWV� 2� *KLVDOED� 7HWUDKHGURQ /HWW�� ��� ����� 1986� 0�<RNR\DPD� 7� 6XJDL� +� 2KWD� 7HWUDKHGURQ� $V\PP�� �� ����� 1993� 7� %HDUG�0�$� &RKHQ� -�6� 3DUUDWW� 1�-� 7XUQHU� -� &URVE\� -� 0RLOOLHW� 7HWUDKHGURQ� $V\PP��

�� ����� 1993��� 0� 6KDSLUD� $�/� *XWPDQ� 7HWUDKHGURQ� $V\PP�� �� ����� 1994��� $� 9RJHO� 3UDFWLFDO 2UJDQLF &KHPLVWU\� � HG�� /RQJPDQ� /RQGRQ� 1978WK

��� 3�%� 5XVVHOO� -� $P� &KHP� 6RF�� ��� ����� 1950��� +� 0F1DE� 2UJ� 6\QWK� ,9� ���� 1963��� 3� &URR\� 5� 'H 1H\V� -� (OLDHUV� 5� /LYH\QV� *� 6LPRQHW� -� 9DQGHYHOGH� %XOO� 6RF�

&KLP� %HOJ�� ��� ���� 1977��� 6�9� 3DWLO� 5�%� 0DQH� 0�0� 6DOXQNKH� &KHP� ,QG�� ��� 1991� 3�3� .XPEKDU� 0�0�

6DOXQNKH� 5�%� 0DQH� ,QG� -� &KHP�� ��%� ���� 1991��� %� 5LJR� '� )DVVHXU� 3� &DXOLH]� '� &RXWXULHU� 7HWUDKHGURQ /HWW�� ��� ����� 1989��� (� )LVFKHU� $� 'LOWKH\� %HU�� ��� ���� 1902��� $� .RW\N� .� -DQDFHN� &HOO 0HPEUDQH 7UDQVSRUW� 3ULQFLSOHV DQG 7HFKQLTXHV� �QG

(G� 3OHQXP 3UHVV� /RQGRQ� 1975��� 5�)� 5HNNHU� 7KH +\GURSKRELF )UDJPHQWDO &RQVWDQW� (OVHYLHU� $PVWHUGDP� 1977�

<� 6DVDNL� +� .XERGHUD� 7� 0DWXV]DNL� +� 8PH\DPD� -� 3KDUPDFRELR�'\QDPLFV�

��� ���� 1991��� $� 5RGD� $� 0LQXWHOOR� 0�$� $QJHOORWWL� $� )LQL� -� /LSLG 5HV�� ��� ����� 1990��� 0� 5HVORZ� 3� $OGHUFUHXW]� %� 0DWWLDVVRQ� $SSO� 0LFURELRO� %LRWHFK�� ��� �� 1987�

7�/� +XDQJ� $� 6]HNDFV� 7� 8HPDWVX� (� .XZDQR� $� 3DUNLQVRQ� %�'� +DPPRFN�

3KDUP� 5HV�� ��� ���� 1993��� 3� -ROOHV� -� -ROOHV� 0RO� &HOO� %LRFKHP�� ��� ���� 1984��� 6� :ROIH� &� )HUUDUL� :�6� /HH� 7HWUDKHGURQ /HWW�� ��� ����� 1969��� 6� 2SSROVNL� $� :HLQEDXP� %HU�� ��� ����� 1914��� $� 0F.HQ]LH� *� 0DUWLQ� +�*� 5XOH� -� &KHP� 6RF�� ����� 1914��� -�&� 6KHHKDQ� '�'�+� <DQJ� -� $P� &KHP� 6RF�� ��� ����� 1958��� (�&� 7D\ORU� -� :ROLQVN\� +�+� /HH� -� $P� &KHP� 6RF�� ��� ����� 1954��� :� 7UHLEV� +� 2UWWPDQQ� %HU�� ��� ���� 1958

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Page 105: University of Groningen Enzymatic preparation of optically

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