Bicyclo[3.2.1]octenones as Building Blocks in Natural Product Synthesis (IV): Formal Synthesis of (±)‐Hydroxyloganin Aglucone

Abstract

A formal synthesis of (±)-hydroxyloganin aglucone from bicyclo13.2.1]octenone 1 is described. Ring opening of syn.8-(metbanesulfonyloxy)-I-phenyltbiotricyclo[4,2.1.0 3 . 1]non-4-en-2-one 14 with potassium hydroxide is the key reaction.

A Versatile Diquinane from Fulvene as a Building Block in Natural Product Synthesis. 1. A Facile Synthesis of the Iridoids Loganin and Sarracenin

“…In the synthesis of iridoid monoterpenes, construction of the cyclopenta[ c ]pyran ring system from a more stable cis -bicyclo[3.3.0]octene precursor in the final stage is an important strategy (Figure ). ,5c,d, Recently, we found that fulvene 9 undergoes a three-carbon annulation to afford diquinane 8 . We believe diquinane 8 is a potential intermediate for the synthesis of iridoid natural products.…”

“…Oxidation of the formyl group in 12 with silver oxide and subsequent esterification of the resulting hydroxy acid with diazomethane afforded hydroxy ester 13 in 92% yield. Since 13 was converted into loganin ( 2 ) previously, this work constitutes a formal total synthesis of racemic loganin ( 2 ). 4a,b

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“…These characteristics elicited widespread interest from synthetic chemists . Among the various iridoid monoterpenes, the cyclopenta[ c ]pyran bearing the 2-oxo- cis -bicyclo[4.3.0]nonane moiety 1 (Figure ) as a fundamental ring system is the most widely distributed including loganin ( 2 ), mussaenoside ( 3 ), mitsugashiwalactone ( 4) , and boschnialactone ( 5 ) . Some iridoid natural products with a C 7 −C 8 seco ring (e.g., sarracenin ( 6 ) and xylomollin ( 7 ) 9 ) have received the attention of synthetic chemists due to their biological activities and the challenge posed by the high degree of functionalization with attendant stereochemical intricacies.…”

Total Synthesis of (±)-Sarracenin

“…Ketone 6 was first transformed to thioether 9. On treatment with aqueous acid, 9 was converted to β-hydroxy ketone 10 , which then reacted with methanesulfonyl chloride in pyridine to give the corresponding mesylate 5 …”