Divergence en route to nonclassical annonaceous acetogenins. Synthesis of pyranicin and pyragonicin.
Syntheses of the nonclassical annonaceous acetogenins, pyranicin, and pyragonicin from common late-stage intermediates are presented. The construction of key elements relies on asymmetric HWE reactions, including the desymmetrization of a meso-dialdehyde and a parallel kinetic resolution of a racemic aldehyde. A stereoconvergent Pd-catalyzed substitution serves to install the C4 stereocenter in protected form with different orthogonal protective groups. A divergent strategy to form 1,4- and 1,6-diols, employing stereoselective Zn-mediated alkynylations, is used for completion of the core structures. Notably, the stereoselective coupling reaction toward pyragonicin proceeds with highly functionalized fragments. The methodology is further expanded by a divergent synthesis of all stereoisomers of the 2,3,6-trisubstituted tetrahydropyran subunit.
KTH Chemical Science and Engineering, Organic Chemistry, SE-100 44 Stockholm, Sweden.
Daniel
D
Strand
Per-Ola
PO
Norrby
Tobias
T
Rein
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000737:chemistry; D054378:Acetogenins; D002384:Catalysis; D003500:Cyclization; D005233:Fatty Alcohols / Q000138:chemical synthesis*; D005663:Furans / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis*; D010984:Platinum / Q000737:chemistry; D011714:Pyrans / Q000737:chemistry; D013237:Stereoisomerism
D054378:Acetogenins; D005233:Fatty Alcohols; D005663:Furans; D007783:Lactones; D011714:Pyrans; C509193:pyragonicin; C475590:pyranicin; D010984:Platinum; C004511:butenolide; D015107:4-Butyrolactone