PMID- 28368003
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20181102
LR  - 20230802
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 8
DP  - 2017 Apr 3
TI  - Enzyme catalysed Pictet-Spengler formation of chiral 1,1'-disubstituted- and 
      spiro-tetrahydroisoquinolines.
PG  - 14883
LID - 10.1038/ncomms14883 [doi]
LID - 14883
AB  - The Pictet-Spengler reaction (PSR) involves the condensation and ring closure 
      between a beta-arylethylamine and a carbonyl compound. The combination of dopamine 
      and ketones in a PSR leads to the formation of 1,1'-disubstituted 
      tetrahydroisoquinolines (THIQs), structures that are challenging to synthesize 
      and yet are present in a number of bioactive natural products and synthetic 
      pharmaceuticals. Here we have discovered that norcoclaurine synthase from 
      Thalictrum flavum (TfNCS) can catalyse the PSR between dopamine and unactivated 
      ketones, thus facilitating the facile biocatalytic generation of 
      1,1'-disubstituted THIQs. Variants of TfNCS showing improved conversions have 
      been identified and used to synthesize novel chiral 1,1'-disubstituted and 
      spiro-THIQs. Enzyme catalysed PSRs with unactivated ketones are unprecedented, 
      and, furthermore, there are no equivalent stereoselective chemical methods for 
      these transformations. This discovery advances the utility of enzymes for the 
      generation of diverse THIQs in vitro and in vivo.
FAU - Lichman, Benjamin R
AU  - Lichman BR
AUID- ORCID: 0000-0002-0033-1120
AD  - Department of Biochemical Engineering, University College London, Gower Street, 
      London WC1E 6BT, UK.
FAU - Zhao, Jianxiong
AU  - Zhao J
AD  - Department of Chemistry, University College London, Christopher Ingold Building, 
      20 Gordon Street, London, WC1H 0AJ, UK.
FAU - Hailes, Helen C
AU  - Hailes HC
AD  - Department of Chemistry, University College London, Christopher Ingold Building, 
      20 Gordon Street, London, WC1H 0AJ, UK.
FAU - Ward, John M
AU  - Ward JM
AD  - Department of Biochemical Engineering, University College London, Gower Street, 
      London WC1E 6BT, UK.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170403
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
PMC - PMC5382262
COIS- The authors declare no competing financial interests.
EDAT- 2017/04/04 06:00
MHDA- 2017/04/04 06:01
PMCR- 2017/04/03
CRDT- 2017/04/04 06:00
PHST- 2017/01/03 00:00 [received]
PHST- 2017/02/08 00:00 [accepted]
PHST- 2017/04/04 06:00 [entrez]
PHST- 2017/04/04 06:00 [pubmed]
PHST- 2017/04/04 06:01 [medline]
PHST- 2017/04/03 00:00 [pmc-release]
AID - ncomms14883 [pii]
AID - 10.1038/ncomms14883 [doi]
PST - epublish
SO  - Nat Commun. 2017 Apr 3;8:14883. doi: 10.1038/ncomms14883.