最近よく見る「骨格編集反応」の一つである光化学環縮小反応を鍵反応として，３種の骨格の異なるトウダイグサジテルペン（レシニフェラトキシン，ユーフォストラノイドB，ペプラノールA）の全合成を行っています。
鍵反応はピリジンの２位と６位を結んで，シクロペンテンとアジリジンに導くという反応で，４，５位に二重結合が入りますから，３位にメトキシ基を入れておくと，生じたシクロペンテンはすべての炭素が官能基化されていることになり，またアジリジンの２つ炭素は不斉炭素なので，立体化学の情報も含むことになります。
合成の全体から見て，さらにおもしろいのは生合成とも関連する転位反応で，異なる炭素骨格に導いているところです。まず，６員環の天然物カルボンから出発し，ピリジン環への桜井反応と環縮小反応で，5-7-6環系を構築します。還元的に脱窒素し，二重結合の一つを選択的にエポキシ化して，セミピナコール転位でシス（仮称）5-6-7環系に変換し，さらに，レトロアルドール/アルドールで，トランス（仮称）5-6-7環系に異性化します。ここからペプラノールAへの骨格変換は，一見メチル基の1,2シフトに見え，生合成経路をそのように推定した人もいたようですが，実はカチオン性[3,4]シグマトロピーです。B環を切断しながら新たなB環をつくるというアクロバティックな反応を，ルイス酸触媒下，好収率で実現しています。
They carried out the total synthesis of three Euphorbia diterpenoids with different carbon skeletons (resiniferatoxin, euphorstranoid B, and pepluanol A), using as the key reaction a photochemical ring contraction, one of the “skeletal editing reactions” frequently seen in recent years.
The key reaction forms a bond between the 2- and 6-positions of a pyridine to give a cyclopentene fused to an aziridine. Because a double bond is installed between the 4- and 5-positions, placing a methoxy group at the 3-position means that every carbon of the resulting cyclopentene is functionalized. In addition, the two aziridine carbons are stereogenic, so the product also carries stereochemical information.
What makes the synthesis as a whole even more interesting is that rearrangement reactions, which are also related to biosynthesis, lead to different carbon skeletons. Starting from the six-membered-ring natural product carvone, a Sakurai reaction on the pyridine ring followed by the ring contraction constructs a 5-7-6 ring system. Reductive denitrogenation and selective epoxidation of one of the double bonds, followed by a semipinacol rearrangement, converts this into the cis (tentative name) 5-6-7 ring system. A retro-aldol/aldol sequence then isomerizes it to the trans (tentative name) 5-6-7 ring system. The skeletal conversion from here to pepluanol A looks at first glance like a 1,2-methyl shift, and some researchers have proposed the biosynthetic pathway on that basis, but it is in fact a cationic [3,4] sigmatropic rearrangement. This acrobatic reaction, in which the B ring is cleaved while a new B ring is formed, is achieved in good yield under Lewis acid catalysis.
Euphorbia Diterpenoids uploaded.
https://www.ohira-sum.com/wp-content/uploads/2026/10/jacs26-37489.pdf
最近よく見る「骨格編集反応」の一つである光化学環縮小反応を鍵反応として，３種の骨格の異なるトウダイグサジテルペン（レシニフェラトキシン，ユーフォストラノイドB，ペプラノールA）の全合成を行っています。
鍵反応はピリジンの２位と６位を結んで，シクロペンテンとアジリジンに導くという反応で，４，５位に二重結合が入りますから，３位にメトキシ基を入れておくと，生じたシクロペンテンはすべての炭素が官能基化されていることになり，またアジリジンの２つ炭素は不斉炭素なので，立体化学の情報も含むことになります。
合成の全体から見て，さらにおもしろいのは生合成とも関連する転位反応で，異なる炭素骨格に導いているところです。まず，６員環の天然物カルボンから出発し，ピリジン環への桜井反応と環縮小反応で，5-7-6環系を構築します。還元的に脱窒素し，二重結合の一つを選択的にエポキシ化して，セミピナコール転位でシス（仮称）5-6-7環系に変換し，さらに，レトロアルドール/アルドールで，トランス（仮称）5-6-7環系に異性化します。ここからペプラノールAへの骨格変換は，一見メチル基の1,2シフトに見え，生合成経路をそのように推定した人もいたようですが，実はカチオン性[3,4]シグマトロピーです。B環を切断しながら新たなB環をつくるというアクロバティックな反応を，ルイス酸触媒下，好収率で実現しています。
They carried out the total synthesis of three Euphorbia diterpenoids with different carbon skeletons (resiniferatoxin, euphorstranoid B, and pepluanol A), using as the key reaction a photochemical ring contraction, one of the “skeletal editing reactions” frequently seen in recent years.
The key reaction forms a bond between the 2- and 6-positions of a pyridine to give a cyclopentene fused to an aziridine. Because a double bond is installed between the 4- and 5-positions, placing a methoxy group at the 3-position means that every carbon of the resulting cyclopentene is functionalized. In addition, the two aziridine carbons are stereogenic, so the product also carries stereochemical information.
What makes the synthesis as a whole even more interesting is that rearrangement reactions, which are also related to biosynthesis, lead to different carbon skeletons. Starting from the six-membered-ring natural product carvone, a Sakurai reaction on the pyridine ring followed by the ring contraction constructs a 5-7-6 ring system. Reductive denitrogenation and selective epoxidation of one of the double bonds, followed by a semipinacol rearrangement, converts this into the cis (tentative name) 5-6-7 ring system. A retro-aldol/aldol sequence then isomerizes it to the trans (tentative name) 5-6-7 ring system. The skeletal conversion from here to pepluanol A looks at first glance like a 1,2-methyl shift, and some researchers have proposed the biosynthetic pathway on that basis, but it is in fact a cationic [3,4] sigmatropic rearrangement. This acrobatic reaction, in which the B ring is cleaved while a new B ring is formed, is achieved in good yield under Lewis acid catalysis.