Synthesis of vinylated hydroxy esters with applicability in signal enhanced magnetic resonance imaging

A a vinyl hydroxy ester of formula (IXa), (IXb) or (IXc),

• wherein
• R′ is selected from H and D, particularly H,
• R8, R9 and R12 are independently of each other selected from H, D, and a fully or partly deuterated alkyl, particularly C1-16-alkyl, more particularly C1-6-alkyl, even more particularly C1-3-alkyl,
• each R10, R13, R15, R17, R19 and R21 is independently of any other R10, R13, R15, R17, R19 or R21 selected from H, D and NH2, wherein the NH2 moiety may be protected by a protecting group, particularly selected from H, D and NH2,
• each R11, R14, R16, R18, R20 and R22 is independently of any other R11, R14, R16, R18, R20 or R22 selected from H and D,
• X1, X2 and X3 are independently of each other H or D, wherein at least one X1, X2 and X3 is D, particularly each of X1, X2 and X3 is D,
• A is —CH3, —CH2D, —CHD2 or —CD3, particularly —CD3, and
• E1, E2, E3, E4 and E5 are independently of each other H, D or
• wherein X1, X2 and X3 are as defined above and wherein at least one moiety selected from E1 and E2 and at least one moiety selected from E3, E4 and E5 is
• m, q, r, s, v and w are independently of each other integers between 0 and 16, particularly between 0 and 6, more particularly between 0 and 3.

An intermediate of formula (VIIIa), (VIIIb) or (VIIIc)

• wherein
• R8, R9 and R12 are independently of each other selected from H, D, and a fully or partly deuterated alkyl, particularly C1-16-alkyl, more particularly C1-6-alkyl, even more particularly C1-3-alkyl,
• each R10, R13, R15, R17, R19 and R21 is independently of any other R10, R13, R15, R17, R19 or R21 selected from H, D and NH2, wherein the NH2 moiety may be protected by a protecting group, particularly selected from H, D and NH2,
• each R11, R14, R16, R18, R20 and R22 is independently of any other R11, R14, R16, R18, R20 or R22 selected from H and D,
• Q is O or N,
• Z is a protecting group, particularly selected from an amine protection group and a photolabile protection group, more particularly selected from, Boc, Fmoc, benzyl carbamate, acetamide, trifluoroacetamide, and
• wherein
• R6 or R7 is H or —OCH3, and
• the other moiety R7 or R6 is selected from H, —OCH3, —O—CH2—C(═O)—O—CH2—CH3, —CH2—C(═O)—CH(Ra)—NH-Boc, —O—[CH2—CH2—O]p—H, —O—CH2—CH(OH)—CH2—OH, —O—CH2—C(═O)—NH—CH2—CH2—NH-Boc, with
• Ra being H or a C1-3-alkyl,
• p being an integer between 0 and 6,
• X1, X2 and X3 are independently of each other H or D, wherein at least one X1, X2 and X3 is D, particularly each of X1, X2 and X3 is D,
• A is —CH3, —CH2D, —CHD2 or —CD3, particularly —CD3, and
• E1, E2, E3, E4 and E5 are independently of each other H, D or
• wherein X1, X2 and X3 are as defined above and wherein at least one moiety selected from E1 and E2 and at least one moiety selected from E3, E4 and E5 is
• m, q, r, s, v and w are independently of each other integers between 0 and 16, particularly between 0 and 6, more particularly between 0 and 3.