Bryostatin compounds and methods of preparing the same

A method of preparing a bryostatin compound, wherein the bryostatin compound is of formula (XXIV)

• wherein
• W1 is an alkenyl, a substituted alkenyl, an alkynyl, a substituted alkynyl, an allenyl, a substituted allenyl, an aryl, a substituted aryl, a heteroaryl, a substituted heteroaryl, an alkyl, a substituted alkyl;
• or
• W1 is a carbon chain comprising oxygen atoms, nitrogen atoms, rings, substituted rings, or a combination thereof;
• Z2 is ═CR5R6 or ═NR7 when the covalent bond “b” is a double bond;
• Z2 is —OR8 or —N(R7)2 when the covalent bond “b” is a single bond;
• X1 is H or OR11;
• Y1 is H or OR12;
• R5, R6, R7 and R8 are each independently H, halogen, alkyloxycarbonyl, substituted alkyloxycarbonyl, alkyl or substituted alkyl;
• R11 is H, an acyl, a substituted acyl, an alkyl, a substituted alkyl, —CO(substituted aryl), CO-aryl, CO-heteroaryl or —CO(substituted heteroaryl);
• R12 is H, an alkyl or a substituted alkyl;
• R13 is H, an alkyl or a substituted alkyl;
• R14 and R15 are independently H, a hydroxyl protecting group or a promoiety;
• and
• R16 is H, an alkyl, a substituted alkyl, —CO(substituted aryl), CO-aryl, CO-heteroaryl or CO(substituted heteroaryl),
• wherein the method comprises:
• (a) preparing a compound of formula (X) from a starting material of formula (I):
• through the use of intermediates of generic formulae (II)-(IX)
• wherein:
• P1 and P2 are independently H or a hydroxyl protecting group or synthetic equivalent thereof;
• each R and R1—R4 is independently H, an alkyl or a substituted alkyl;
• R12 is H, an alkyl or a substituted alkyl;
• and
• R11 is an acyl, a substituted acyl, an alkyl, a substituted alkyl, —CO-aryl, —CO(substituted aryl), —CO-heteroaryl, or —CO(substituted heteroaryl);
• and each X is a leaving group;
• (b) preparing a compound of formula (XX) from a starting material of formula (XI):
• through the use of intermediates of generic formulae (XII)-(XIII), (XIVa), (XIVb), and (XIV)-(XIX)
• wherein:
• Z1 is an alkynyl, a substituted alkynyl, an allenyl, a substituted allenyl an alkyl or a substituted alkyl;
• R3, R12, R13 and R16 are independently H, an alkyl or a substituted alkyl;
• and
• P3 is H or a hydroxyl protecting group;
• and
• (c) coupling the compound of formula (X) and the compound of formula (XX) via esterification and macrocyclization (or vice versa) to produce a macrocyclic compound.