Asymmetric synthesis and uses of compounds in disease treatments

A method for stereospecifically preparing a substantially pure diastereomeric compound of formula (I):

• or a salt thereof,
• wherein the substantially pure diastereomeric compound has a diastereomeric excess (de) of no less than 99%,
• wherein
• R1 is —OH, —OC(O)—R1a or —OC(O)R1bCOOH and R4 is —OH, —OC(O)—R4a or —OC(O)R4bCOOH, wherein R1a and R4a are independently hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl, and R1b and R4b are independently-C1-C6alkyl- or —C2-C6alkenyl-;
• R2 and R5 are —C≡CH;
• R6 and R7 are independently C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl;
• R8 and R9 are independently hydrogen, —OH, —NH2, —NO2, halogen, C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C14 aryl, 5-6-membered heteroaryl or 3-6 membered heterocyclyl,
• comprising:
• (a) reacting a di-ketone compound of formula (II)
• with a silylacetylene of formula (III)
• wherein Ra, Rb and Rc are independently selected from the group consisting of C1-C20 alkyl optionally substituted by —OH, halogen or C1-C6alkyl, C1-C6alkoxy optionally substituted by —OH, halogen or C1-C6 alkyl, C3-C6 cycloalkyl, C6-C14 aryl, 5-6-membered heteroaryl or 3-6 membered heterocyclyl,
• in the presence of an organometallic reagent R10-M, wherein M is Li, Na or K, and R10 is C1-C20alkyl, optionally substituted by —OH, halogen or C1-C6alkyl,
• to form an intermediate of the structure