An Efficient Synthesis of Cerbinal, a 10 π Aromatic Iridoid

Abstract

Cerbinal, an unusual iridoid with 10 π-System, was synthesized from (+)-genipin in 6 steps via dehydration of the hemiacetal and subsequent dehydrogenation with DDQ.

Cyclopenta[c]pyrans

“…The first synthesis of cerbinal 12 from (+)‐genipin 5 proceeded over six steps in 24% overall yield [40]; it was later resumed in a more efficient protocol (Scheme ) [8]. Silylation of 5 with t ‐butyldimethylsilyl chloride (TBSCl) in the presence of imidazol quantitatively gave the monosilyl ether 28 .…”

Synthetic Studies toward Plumisclerin A

“…P lumisclerin A was isolated and characterized in 2010 by Reyes and co-workers from the samples of the soft coral Plumigorgia teminosclera collected at Mayotte Island. 1 As a novel xenicane-related marine diterpenoid, it possess seven stereogenic centers, including two all-carbon quaternary stereocenters, and an unprecedented tricyclo[4,3,1,0 1,5 ]decane skeleton. Besides its structural complexity, plumisclerin A exhibits moderate cytotoxic activities against several human tumor cell lines, including lung cancer A549 cells (GI 50 = 4.8 μM), colon cancer HT29 cells (GI 50 = 2.1 μM) and breast cancer MDA-MB-231 cells (GI 50 = 6.1 μM).…”

“…1 Its intriguing structure and medicinal potential render it an attractive and challenging target for synthetic chemists. In 2015, Yao and coworkers reported the synthesis of tricyclo[4,3,1,0 1,5 ]decane core of plumisclerin A using a Pauson−Khand annulation and SmI 2 -mediated radical cyclization. 2a Recently, the first and enantioselective total synthesis of plumisclerin A have been achieved in 27 longest linear steps by the same group.…”

“…A key intermolecular Diels−Alder disconnection of the aldehyde 3 would split it into diene 5 and the known dienophile 4. 4 Consequently, we identified commercially available iridoid genipin 6 (∼$5/g) 5 as the starting material for synthesizing diene 5. As demonstrated in Scheme 1, our synthesis commenced with the preparation of known compound 7 starting from inexpensive iridoid genipin.…”

“…The initial attempts under typical conditions (SmI 2 /HMPA/t-BuOH, 7b SmI 2 /MeOH, 7d SmI 2 /t-BuOH, 2a SmI 2 /LiBr/ HFIP, 7k between −78 °C and 0 °C) all failed to give the desired product 16. Much to our delight, we smoothly isolated the cyclized product 16 containing tricyclo[4,3,1,0 1,5 ]decane motif in 50% yield by slowly adding the aldehyde 2 to a refluxing solution of SmI 2 in THF in the absence of any additives, 15 indicating that the elevated temperature was essential to forge the strained cyclobutane ring. Moving In summary, we have developed a concise and efficient approach for building the core tetracyclic carbon skeleton of plumisclerin A.…”