Abstract:
:Tramadol, previously only known as a synthetic analgesic, has now been found in the bark and wood of roots of the African medicinal tree Nauclea latifolia. At present, no direct evidence is available as to the biosynthetic pathway of its unusual skeleton. To provide guidance as to possible biosynthetic precursors, we have adopted a novel approach of retro-biosynthesis based on the position-specific distribution of isotopes in the extracted compound. Relatively recent developments in isotope ratio monitoring by (13)C NMR spectrometry make possible the measurement of the nonstatistical position-specific natural abundance distribution of (13)C (δ(13)Ci) within the molecule with better than 1‰ precision. Very substantial variation in the (13)C positional distribution is found: between δ(13)Ci = -11 and -53‰. Distribution is not random and it is argued that the pattern observed can substantially be interpreted in relation to known causes of isotope fractionation in natural products. Thus, a plausible biosynthetic scheme based on sound biosynthetic principals of precursor-substrate relationships can be proposed. In addition, data obtained from the (18)O/(16)O ratios in the oxygen atoms of the compound add support to the deductions made from the carbon isotope analysis. This paper shows how the use of (13)C NMR at natural abundance can help with proposing a biosynthetic route to compounds newly found in nature or those difficult to tackle by conventional means.
journal_name
Proc Natl Acad Sci U S Aauthors
Romek KM,Nun P,Remaud GS,Silvestre V,Taïwe GS,Lecerf-Schmidt F,Boumendjel A,De Waard M,Robins RJdoi
10.1073/pnas.1506011112subject
Has Abstractpub_date
2015-07-07 00:00:00pages
8296-301issue
27eissn
0027-8424issn
1091-6490pii
1506011112journal_volume
112pub_type
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