Synthesis of desosamines

A method of preparing a compound of Formula (B):

• or salt thereof, comprising cyclizing an alcohol of Formula (A):
• or salt thereof, with glyoxal:
• wherein:
• R1 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORS, —N(RS)2, —NRS(ORS), —SRS, —SSRS, —Si(RS)3, —OSi(RS)3, or of formula:
• each of R2 and R3 is independently hydrogen, halogen, optionally substituted C1-C6 alkyl, —ORSO, or —N(RSN)2;
• LS1 is a bond, —NRS—, —O—, or —S—, or a linking group selected from the group consisting of optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted heteroalkenylene, and optionally substituted heteroalkynylene, and combinations thereof;
• XS is a bond, —C(═O)—, —C(═NRSN)—, —S(═O)—, or —S(═O)2—;
• LS2 is a bond, —NRS—, —O—, or —S—, or a linking group selected from the group consisting of optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted heteroalkenylene, and optionally substituted heteroalkynylene, and combinations thereof;
• each RS is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or a sulfur protecting group when attached to a sulfur atom, or two RS attached to the same nitrogen atom are taken together to form ═N2, an optionally substituted heterocyclyl, or heteroaryl ring;
• each RSN is independently hydrogen, optionally substituted C1-C6 alkyl, or a nitrogen protecting group, or two RSN attached to the same nitrogen atom are joined to form an optionally substituted heterocyclyl or heteroaryl ring;
• each of R4a and R4b is independently hydrogen, halogen, optionally substituted C1-C6 alkyl, or —ORSO;
• and
• each RSO is independently hydrogen, optionally substituted C1-C6 alkyl, a carbohydrate, or an oxygen protecting group.

A method of preparing a compound of Formula (C′):

• or salt thereof, comprising reducing a compound of Formula (B′):
• or salt thereof, wherein:
• R1 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORS, —N(RS)2, —NRS(ORS), —SRS, —SSRS, —Si(RS)3, —OSi(RS)3, or of formula:
• each of R2 and R3 is independently hydrogen, halogen, optionally substituted C1-C6 alkyl, —ORSO, or —N(RSN)2;
• LS1 is a bond, —NRS—, —O—, or —S—, or a linking group selected from the group consisting of optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted heteroalkenylene, and optionally substituted heteroalkynylene, and combinations thereof;
• XS is a bond, —C(═O)—, —C(═NRSN)—, —S(═O)—, or —S(═O)2—;
• LS2 is a bond, —NRS—, —O—, or —S—, or a linking group selected from the group consisting of optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted heteroalkenylene, and optionally substituted heteroalkynylene, and combinations thereof;
• each RS is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or a sulfur protecting group when attached to a sulfur atom, or two RS attached to the same nitrogen atom are taken together to form ═N2, an optionally substituted heterocyclyl, or heteroaryl ring;
• each RSN is independently hydrogen, optionally substituted C1-C6 alkyl, or a nitrogen protecting group, or two RSN attached to the same nitrogen atom are joined to form an optionally substituted heterocyclyl or heteroaryl ring;
• each of R4a and R4b is independently hydrogen, halogen, optionally substituted C1-C6 alkyl, or —ORSO;
• R5 and R6 are hydrogen;
• and
• RSO is independently hydrogen, optionally substituted C1-C6 alkyl, a carbohydrate, or an oxygen protecting group.