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OpenSourceMalaria / Series4

Repository for Series 4 of the Open Source Malaria Consortium
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The Phenylalaninol ether has been successfully synthesised #30

Closed edwintse closed 6 years ago

edwintse commented 6 years ago

The Phenylalaninol ether is key compound for the series originally proposed to investigate the ether chain length (#254). The synthesis of the compound was initially attempted by @JoannaUbels in 2014 by direct coupling of (R)-2-amino-3-phenylpropan-1-ol to the core, however the reaction was unsuccessful (ELN). Boc protection wasn't attempted due to time constrains. Most recently, this compound was picked up by Griffith Uni (#523) but again, time constraints meant the compound wasn't synthesised.

I have carried out the synthesis by Boc protecting the amine, SN2 displacement with the core and deprotecting under acidic conditions. The synthesis was done on both (R)- and (S)-enantiomers of the starting material. untitled wiley-3 ELN entries for (R)/(S) Boc protection, (R)/(S) SN2 displacement and (R)/(S) Boc deprotection.

(R)-Boc protected 1H,13C,19F and LRMS (pdfs attached). (S)-Boc protected 1H,13C,19F and LRMS (pdfs attached). (R)-free amine 1H,13C,19F and LRMS (pdfs attached). (S)-free amine 1H,13C,19F and LRMS (pdfs attached).

n.b. NMRs of the free amines were done in MeOD so the amine signals are absent. Will need to also get optical rotation for these.

The 4 final compounds (both Boc protected and both free amines) will be sent off for biological evaluation in the next batch.

Removed from the DCNYS section of the wiki Side chain derived from phenylalanine: GHI 254, ELN, OSM-S-261, Griffith Uni proposed synthesis
ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCH(N)CC4=CC=CC=C4)N32 InChI=1S/C20H18ClN5O/c21-16-8-6-15(7-9-16)20-25-24-18-11-23-12-19(26(18)20)27-13-17(22)10-14-4-2-1-3-5-14/h1-9,11-12,17H,10,13,22H2/t17-/m1/s1

Phenylalaninol ether analogues

Strings

(R)-Boc protected FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC@H=O)CC4=CC=CC=C4)N32 InChI=1S/C26H27F2N5O4/c1-26(2,3)37-25(34)30-19(13-17-7-5-4-6-8-17)16-35-22-15-29-14-21-31-32-23(33(21)22)18-9-11-20(12-10-18)36-24(27)28/h4-12,14-15,19,24H,13,16H2,1-3H3,(H,30,34) SDPYEXOSVNFLTG-UHFFFAOYSA-N

(S)-Boc protected FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC@@H=O)CC4=CC=CC=C4)N32 InChI=1S/C26H27F2N5O4/c1-26(2,3)37-25(34)30-19(13-17-7-5-4-6-8-17)16-35-22-15-29-14-21-31-32-23(33(21)22)18-9-11-20(12-10-18)36-24(27)28/h4-12,14-15,19,24H,13,16H2,1-3H3,(H,30,34) SDPYEXOSVNFLTG-UHFFFAOYSA-N

(R)-free amine FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC@HCC4=CC=CC=C4)N32 InChI=1S/C21H19F2N5O2/c22-21(23)30-17-8-6-15(7-9-17)20-27-26-18-11-25-12-19(28(18)20)29-13-16(24)10-14-4-2-1-3-5-14/h1-9,11-12,16,21H,10,13,24H2/t16-/m1/s1 FXPPGJNSMWQGRD-MRXNPFEDSA-N

(S)-free amine FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC@@HCC4=CC=CC=C4)N32 InChI=1S/C21H19F2N5O2/c22-21(23)30-17-8-6-15(7-9-17)20-27-26-18-11-25-12-19(28(18)20)29-13-16(24)10-14-4-2-1-3-5-14/h1-9,11-12,16,21H,10,13,24H2/t16-/m0/s1 FXPPGJNSMWQGRD-INIZCTEOSA-N

edwintse commented 6 years ago

Compound has been removed from the DCNYS section (text copied over above).

edwintse commented 6 years ago

Closing, but will continue to upload the remaining data for completeness.

mcoster commented 6 years ago

I realise this is now closed, but belated congrats Ed!