i-methoxyphenylalanine 4 could possibly be obtained simiThe third unusual amino acid, -methoxyphenylalanine ,,, could be obtained similarly for the tryptophan constructing block (Scheme 13). Protected (R)-serine 65 was lowered the tryptophan Protected 1 larly for the tryptophan building block (Scheme 13). Protected (R)-serine 65 was lowered towards the corresponding aldehyde, which was subjected to a chelate-controlled aryl-metal the corresponding aldehyde, which was subjected to a chelate-controlled aryl-metal toMar. Drugs 2021, 19,15 ofMar. Drugs 2021, 19, x FOR PEER REVIEW16 ofto the corresponding aldehyde, which was subjected to a chelate-controlled aryl-metal addition. The addition of phenylmagnesium bromide offered an acceptable yield but addition. The addition of phenylmagnesium bromide provided an acceptable yield but only moderate diastereoselectivity (7:three). In contrast, within the presence of titanium salts, the only moderate diastereoselectivity (7:three). In contrast, CysLT1 drug inside the presence of titanium salts, the preferred coupling solution 66 might be obtained as assingle diastereomer in enantiomerically preferred coupling item 66 could be obtained a a single diastereomer in enantiomerically kind.kind. Further common transformations yielded constructing block 32. pure pure Further regular transformations yielded creating block 32.Scheme 13. Synthesis of -methoxyphenylalanine derivatives (constructing block ). Scheme 13. Synthesis of -methoxyphenylalanine derivatives (creating block 4 ).An alternative protocol, which also permitted the synthesis of substituted developing substituted blocks, was developed beginning from commercially offered chloramphenicol base 67 (Scheme 13) [73]. As a result, the amino diol was 1st converted stepwise in to the protected Thus, the amino 1st derivative 68a. The nitro functionality could conveniently be lowered to to the corresponding ani68a. The nitro functionality could easily be decreased the corresponding aniline derivative 68b, 68b, a perfect candidate for further structural variations by way of diazonium line derivative an ideal candidate for further structural variations by means of diazonium chemistry. Depending on the reaction circumstances and additives additives utilized, numerous new derivachemistry. According to the reaction situations and employed, numerous new derivatives 68c-e could be obtained, which could possibly be oxidized to oxidized towards the corresponding amino acids tives 68c-e may be obtained, which could possibly be the corresponding amino acids 69a-d, while deamination of 68b provided the unsubstituted developing block 32. 69a-d, whilst deamination of 68b provided the unsubstituted constructing block 32. 7 For the synthesis of your fourth, the CDK14 Compound unsaturated amino acid , also a chelate enolate Claisen rearrangement, was used beginning with chiral ester 70 (Scheme 14) [746]. Rearrearrangement, was made use of beginning with chiral ester (Scheme Rearrangement of the corresponding zinc enolate proceeded with complete chirality transfer and high stereoselectivity, and ester was obtained after O-methylation. Ozonolysis proand higher stereoselectivity, and ester 7171 was obtained just after O-methylation. Ozonolysis offered desired aldehyde, which was subjected to a to a Wittig reaction. However, tiny vided the the desired aldehyde, which was subjected Wittig reaction. Even so, onlyonly tiny amounts of the desired item be obtained, even even huge large from the with the amounts with the desired item couldcould be obtained,with awith aexcess excess Wittig Wittig reagents, also triggered caused the
