itution step. The very best preferred conformation on the benzylic carbenium ion in outcome can be Bim site explained by a preferred conformation on the benzylic carbenium ion in theO-methylation offered selectivities have been obtained with the tert-butylamide. Subsequent substitution step. The bestmethoxy derivative 31, convertedthe tert-butylamide. Subsequent acid 32 beneath standthe selectivities were obtained with in to the N-Boc-protected amino O-methylation provided the methoxy derivative 31, converted into the N-Boc-protected amino acid 32 under ard conditions. Cereblon custom synthesis common situations.Scheme 7. Synthesis of protected -methoxy phenylalanine 32 (building block 4 ). Scheme 7. Synthesis of protected -methoxy phenylalanine 32 (developing block ).Ultimately, the unsaturated amino acid was obtained through an asymmetric chelate enolate Finally, the unsaturated amino acid 7 was obtained via an asymmetric chelate enolate Claisen rearrangement, created by Kazmaier et al. (Scheme eight) [54,55]. TrifluoroaClaisen rearrangement, developed by Kazmaier et al. (Scheme 8) [54,55]. Trifluoroacetyl cetyl (TFA)-protected glycine crotyl ester deprotonated and converted into a chelated alu(TFA)-protected glycine crotyl ester 33 was 33 was deprotonated and converted into a chelated aluminum ester enolate, which in the presence of quinidine a [3,3]-sigmatropic reminum ester enolate, which inside the presence of quinidine underwentunderwent a [3,3]-sigmatropic rearrangement to amino acid 34 with acid yield and enantioselectivity. Epimerarrangement to unsaturated unsaturated amino good34 with fantastic yield and enantioselectivity. with the -stereogenic center was avoided by was avoided by 1st the Boc-protected ization Epimerization of your -stereogenic center very first converting 34 intoconverting 34 into ester 35 after which, within a second step, into the corresponding phthaloyl-protected derivative the Boc-protected ester 35 after which, within a second step, in to the corresponding phthaloyl36. A direct epimerization-free conversion (34 to 36) was not doable. Ozonolysis of your protected derivative 36. A direct epimerization-free conversion (34 to 36) was not doable. Ozonolysis from the double bond and subsequent Wittig reaction made protected amino acid 37, finally converted into the Fmoc-protected acid 38.Mar. Drugs 2021, 19,Ultimately, the unsaturated amino acid was obtained through an asymmetric chelate enolate Claisen rearrangement, developed by Kazmaier et al. (Scheme eight) [54,55]. Trifluoroacetyl (TFA)-protected glycine crotyl ester 33 was deprotonated and converted into a chelated aluminum ester enolate, which inside the presence of quinidine underwent a [3,3]-sigmatropic rearrangement to unsaturated amino acid 34 with good yield and enantioselec11 of 27 tivity. Epimerization from the -stereogenic center was avoided by initially converting 34 in to the Boc-protected ester 35 after which, inside a second step, into the corresponding phthaloylprotected derivative 36. A direct epimerization-free conversion (34 to 36) was not feasible. Ozonolysis on the double bond and subsequent Wittig reaction produced acid 37, amino double bond and subsequent Wittig reaction created protected aminoprotectedfinally acid 37, finally converted in to the acid 38. converted in to the Fmoc-protectedFmoc-protected acid 38.Scheme 8. Synthesis of protected dehydroamino acid 38 (constructing block 7 ). Scheme eight. Synthesis of protected dehydroamino acid 38 (creating block ).After the desired developing blocks were produced, the synthesis of cyclomarin C and es