Chemical studies towards the synthesis of janolusimide, a marine neurotoxin from janolus cristatus / Nurulhuda Kamaruddin
Janolusimide 19 was chosen to be the synthetic target molecule due to having a unique tripeptide structure besides showing a neurotoxin activity. Our synthetic approach towards the synthesis of janolusimide involved the construction of a core lactam system derived from L-valine using EDC.HCl fol...
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| Format: | Book Section |
| Language: | English |
| Published: |
Institute of Graduate Studies
2017
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| Online Access: | http://ir.uitm.edu.my/id/eprint/18952/ http://ir.uitm.edu.my/id/eprint/18952/1/ABS_NURULHUDA%20KAMARUDDIN%20TDRA%20VOL%2012%20IGS%2017.pdf |
| Summary: | Janolusimide 19 was chosen to be the synthetic target molecule due
to having a unique tripeptide structure besides showing a neurotoxin
activity. Our synthetic approach towards the synthesis of janolusimide
involved the construction of a core lactam system derived from
L-valine using EDC.HCl followed by dimethylation using four different
conditions. Dimethylation at C-3 position of 133 affords (5S)-3,3-
dimethyl-5-isopropylpyrrolidine-2,4-dione 26 in 72% yield using TBAF
as a phase transfer catalyst. In this dimethylation step, a characteristic of
ambident anion also can be observed. Multiple positions of alkylation had
occurred due to enolate’s ambident character of which C,O-alkylated and
O-alkylated side products were observed. While the effort to synthesize
the dipeptide chain was carried out using aldol reaction, N-alkylation of
26 and N-acylation of a template, 2-pyrrolidinone 139 and lactam 26 with
several electrophiles. Four general protocols (Method A-D) to N-acylate
2-pyrrolidinone and lactam 26 were examined.. |
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