Synthesis of the C1-side chain of zaragozic acid D and progress towards a total synthesis

Synthesis of More Highly Oxidized Alkyl Citrates via Direct Regio- and Stereoselective Oxidation

“…We initially targeted L-731,128 ( 3 ) to assign the C10 stereochemistry of the common alkyl side chain. Our retrosynthesis (Scheme ) involves installation of the E -terminal styrene by a stereoselective HWE reaction toward the end of the synthesis and cross metathesis followed by reduction to construct the C6–C7 bond. Myers’ diastereoselective alkylation would give access to both syn - and anti -10,12-dimethyl stereoisomers 12 and 13 , enabling confirmation of the stereochemistry.…”

“…Olefin cross metathesis mediated by a Grubbs–Hoveyda second-generation catalyst in the presence of 2,6-dichloro-1,4-benzoquinone to thwart alkene isomerization , followed by alkene reduction and concomitant benzyl ether hydrogenolysis afforded extended diol 21 in good yield over two steps. DMP oxidation of the primary alcohol and treatment of the crude aldehyde with the anion derived from phosphonate 22 under modified conditions , afforded the desired styrene 23 with excellent stereochemical control (>95:5 E : Z ratio).…”

A General Access to Zaragozic Acids: Total Synthesis and Structure Elucidation of Zaragozic Acid D and Formal Syntheses of Zaragozic Acids A and C

“…[8,9] A comparison with the structures of 1 a and 1 b suggested that the syn configuration in the alkyl side chain of these acids was most likely for 1 c as well. Retrosynthetically, compound 1 c was traced back to propargylic alcohol 2, which in turn could be prepared from terminal alkyne 3, which should be available from the heteroA C H T U N G T R E N N U N G bicyclic compound 4 (Scheme 1).…”