Phosphatidylalkanol homologues having labelled moieties

A method for the preparation of an isotopically labelled phosphatidylalkanol homologue, wherein the method comprises or consists of

• mI(1) preparation of isotopically labelled 1-alkyoyl-2-alkenoylglycerol comprising or consisting of
• mIa1) providing labelled glycerol in which some or all hydrogen atoms have been replaced with deuterium, or
• mIa2) providing labelled glycerol in which some or all carbon atoms have been replaced with 13C-isotopes, or
• mIa3) providing labelled glycerol in which some or all hydrogen atoms have been replaced with deuterium, and some or all carbon atoms have been replaced with 13C-isotopes;
• or
• mIa4) providing unlabelled glycerol;
• mIb) protecting two of the OH/OD-groups of the glycerol moiety;
• mIc) protecting the remaining OH/OD-group in 3-position with a protecting group;
• mId) deprotecting the first two OH/OD-groups;
• mIe) addition of a C12 to C18 saturated alkyl chain to a sn-1 position of the glycerol moiety;
• mIf) addition of a mono-, di-, tri- and tetra-unsaturated chain to a sn-2 position of the glycerol moiety;
• mIg) removing the second protective group;
• mI(2) reacting the isotopically labelled 1-alkyloyl-2-alkenoylglycerol product
• of (1) with a phosphorylation reagent comprising
• (i) if an unlabelled glycerol is provided in mIa4), a labelled alkanol group;
• wherein all or some of the hydrogen atoms of the alkanol residue are replaced by deuterium and/or wherein some or all the carbon atoms of the alkanol residue are replaced by 13C-isotopes or
• a labelled fatty acid chain, wherein all or some of the hydrogen atoms are replaced by deuterium and/or wherein some or all the carbon atoms of the alkanol residue are replaced by 13C-isotopes;
• ii) if a labelled glycerol is provided in mIa1), mIa2) or mIa3), an unlabelled alkanol group, wherein no atom of the alkanol residue has been replaced by deuterium and/or 13C;
• mIh) optionally, removing a protecting agent, if present on the phosphorylation agent;
• mIi) optionally, converting the product to a salt-form of the product.

A method for the preparation of an isotopically labelled phosphatidylalkanol homologue, wherein the method comprises or consists of:

• mIIa1) providing labelled glycerol in which some or all hydrogen atoms have been replaced with deuterium, or
• mIIa2) providing labelled glycerol in which some or all carbon atoms have been replaced with 13C-isotopes, or
• mIIa3) providing labelled glycerol in which some or all hydrogen atoms have been replaced with deuterium, and some or all carbon atoms have been replaced with 13C-isotopes;
• or
• mIIa4) providing unlabelled glycerol;
• mIIb) protecting two of the OH/OD-groups of the glycerol moiety;
• mIIc) protecting the remaining OH/OD-group in the 3-position with a protecting group;
• mIId) deprotecting the first two OH/OD-groups;
• mIIe) addition of a C12 to C18 saturated alkyl chain to a sn-1 position of the glycerol moiety, or
• addition of a labelled C12 to C18 saturated alkyl chain to the sn-1 position of the glycerol moiety;
• mIIf) protecting the hydroxyl-group in 2-position;
• mIIg) removal of the first protection group;
• mIIh) coupling the protected isotopically labelled protected 1-acylglyerol product of mIIg) with a phosphorylation reagent comprising
• i) if an unlabelled glycerol is provided in mIa4), a labelled alkanol group;
• wherein all or some of the hydrogen atoms of the alkanol residue are replaced by deuterium and/or wherein some or all the carbon atoms of the alkanol residue are replaced by 13C-isotopes or
• a labelled fatty acid is introduced to the sn-1 position;
• ii) if a labelled glycerol is provided in mIa1), mIa2) or mIa3), an unlabelled alkanol group, wherein no atom of the alkanol residue has been replaced by deuterium and/or 13C;
• mIIi) deprotecting the hydroxyl group in 2-position;
• mIIj) addition of a mono-, di-, tri- and tetra-unsaturated chain to the sn-2 position of the glycerol moiety;
• mIIh) optionally, removing a protecting agent, if present on the phosphorylation agent;
• mIIi) optionally, converting the product to a salt-form of the product.