Total Synthesis of the Phenolic Steroid Myrmenaphthol A

Abstract

Myrmenaphthol A is a structurally unique phenolic steroid with a naphthyl AB-ring system and an unusual C2 hydroxy group. Herein, we report the first total synthesis of this natural product in 10 steps from inexpensive, commercially available sitolactone. Key features of the synthesis include a Baran decarboxylative coupling and a Friedel–Crafts cyclization/olefin isomerization/aromatization cascade that rapidly assembled the tetracyclic core framework. This synthetic strategy is expected to be readily amenable to the synthesis of other phenolic steroids.

Asymmetric Total Synthesis of the Rearranged Steroid Phomarol Enabled by a Biomimetic SN2′ Cyclization

“…Our retrosynthetic analysis, outlined in Scheme , was guided largely by Jung’s biosynthetic proposal for the formation of the TPR, as well as by our interest in utilizing sitolactone ( 20 ) as a chiral pool starting material for the construction of 6/5-fused ring systems . To maximize the synthetic efficiency, we sought to build the pentacyclic core framework by means of a convergent fragment-coupling approach .…”

Access toward steroid skeleton and its derivatives via copper‐catalyzed intramolecular cyclization: A short synthesis of estradiol and estrone

“…[15] Previously, our group reported two examples for substrates of ene-yne-aldehydes leading to [6,7,5]-tricyclic compounds. [16] Furthermore, by small variation of enyne part this protocol was also extended towards the total synthesis of Taxamairin B and Rosmardiophenol as a [6,7,6] tricyclic core via gold catalyzed cyclization. However, the number of carbon chains was increased to give 1,7-enynals in the place of previously reported 1,6-enynals.…”

“…According to the mechanistic study of our group previously reported work the number of rings can be adjusted by increasing the carbon chain of the enyne-al unit (Figure 3). [17] However, to need [6,6,6] tricyclic compounds via [4 + 2] cycloaddition reaction, recently we studied the cyclization of 2-alkynylphenylcarbonyls (3) with a pendant double bond under gold and copper catalyst. In this study with failure to get [6,6,6]-tricyclic compound through gold catalyzed reaction by varying temperature and solvent, we found Cu(OTf) 2 as a best catalyst to underwent [4 + 2] cycloaddition via intermediate B (Figure 3).…”

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A practical and efficient approach leading to [6,6,6,5] tetracyclic fused ring steroid skeletons (8 a-i) has been designed through copper catalyzed intramolecular [4 + 2] cycloaddition reaction of enyne-carbonyl substrates (7 a-i). The compound 8 a having OMe group at aromatic ring was further utilized to synthesize estradiol and Estrone.

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Asymmetric Total Synthesis of Twin Bufogargarizins A and B

“…In summary, we have achieved the first and asymmetric total synthesis of twin bufogargarizins A and B in 28 and 30 steps, respectively, from commercially available sitolactone . Remarkably, the synthetically challenging [7–5–6–5] tetracyclic core of bufogargarizin A was made efficiently by a unique intramolecular Ru-catalyzed [5 + 2] cycloaddition reaction.…”