The key feature is “skeletal editing” via hydrodealkenation, which combines three classical reactions: ozonolysis, deacylation, and an intramolecular Mannich reaction. This process occurs efficiently in a one-pot system and results in an interesting skeletal transformation. Since the process yields a common substructure among numerous aconitine-related compounds, it may be applicable to the modular synthesis of the aconitine family.
Complex carbon skeletons can also be constructed using reactions described in textbooks, such as pinacol coupling, one-carbon ring expansion using TMS diazomethane, intramolecular DA reactions, Claisen rearrangements, and ring-closing metathesis.
The authors emphasize that introducing a nitrogen-containing quaternary chiral center at an early stage, via the addition of hydrogen cyanide to an allenic compound, made the synthesis efficient. The feasibility of asymmetric synthesis is an interesting point.
Proline and serine derivatives undergo radical coupling to form a carbon skeleton. This process leads to a key intermediate via C-H amination cyclization. Many of these reactions occur in a single pot, enabling a single researcher to synthesize over 9 g of the intermediate in three days. The ideality is 71%. This intermediate can be converted into numerous related natural products in just a few steps. This is truly impressive work by Professor Baran.
Additionally, the first synthesis of neo-STX has been achieved. Although the final route is short, it appears to be the result of considerable effort, such as timing the nitrogen oxidation and protecting the hydroxylamine.
The practical synthesis of the starting material, 4-hydroxyproline, is also significant. Genetically modifying a promising oxidase increased the yield from proline to 61%.
This is truly hybrid natural product synthesis, incorporating radical reactions, late-stage oxidation, and biological methods.
Giraldine I and Heterophyllisine uploaded.
https://www.ohira-sum.com/wp-content/uploads/2025/11/jacs25-37012.pdf
ヒドロデアルキル化による”骨格編集”が最大の特徴です。古典的な反応（オゾン分解，デアシル化，分子内マンニッヒ反応）の組み合わせですが，ワンポットで収率よく進行し，面白い骨格変換になっています。数多くあるアコニチン関連化合物で共通の部分構造なので，モジュラー合成に利用できるかも。
他にもピナコールカップリング，TMSジアゾメタンによる一炭素環拡大反応，分子内DA反応，クライゼン転位，閉環メタセシスなど教科書に出てきそうな反応で複雑な炭素骨格を構築しています。
アレンへのシアン化水素付加で，初期の段階で窒素原子を含む四不斉中心部分を作った事が効率的合成に繋がったことも，著者は強調しています。不斉合成が可能かが気になります。
The key feature is “skeletal editing” via hydrodealkenation, which combines three classical reactions: ozonolysis, deacylation, and an intramolecular Mannich reaction. This process occurs efficiently in a one-pot system and results in an interesting skeletal transformation. Since the process yields a common substructure among numerous aconitine-related compounds, it may be applicable to the modular synthesis of the aconitine family.
Complex carbon skeletons can also be constructed using reactions described in textbooks, such as pinacol coupling, one-carbon ring expansion using TMS diazomethane, intramolecular DA reactions, Claisen rearrangements, and ring-closing metathesis.
The authors emphasize that introducing a nitrogen-containing quaternary chiral center at an early stage, via the addition of hydrogen cyanide to an allenic compound, made the synthesis efficient. The feasibility of asymmetric synthesis is an interesting point.
Saxitoxin and related natural products uploaded.
https://www.ohira-sum.com/wp-content/uploads/2025/11/nat25-646-351.pdf
プロリンとセリンの誘導体をラジカルカップリングさせて炭素骨格をつくり，C-Hアミノ化環化で多くのSTXに変換できる重要中間体に導きます。多くの反応がワンポットで行われ，一人で３日間に９ｇ以上合成できたとのこと。アイデアリティ71% 。多くの関連天然物がここから数段階で合成できます。さすがBaran先生。
加えてネオSTXの初合成も達成しています。最終的には短工程ですが，窒素の酸化のタイミングとかヒドロキシルアミンの保護とか相当な苦労の結果のようです。
原料となる4-ヒドロキシルプロリンの実用的合成も重要で，有望な酸化酵素を改変して，プロリンからの収率を61％まで上げています。
ラジカル反応，後期酸化，生物的手法とまさにハイブリッド天然物合成です。
Proline and serine derivatives undergo radical coupling to form a carbon skeleton. This process leads to a key intermediate via C-H amination cyclization. Many of these reactions occur in a single pot, enabling a single researcher to synthesize over 9 g of the intermediate in three days. The ideality is 71%. This intermediate can be converted into numerous related natural products in just a few steps. This is truly impressive work by Professor Baran.
Additionally, the first synthesis of neo-STX has been achieved. Although the final route is short, it appears to be the result of considerable effort, such as timing the nitrogen oxidation and protecting the hydroxylamine.
The practical synthesis of the starting material, 4-hydroxyproline, is also significant. Genetically modifying a promising oxidase increased the yield from proline to 61%.
This is truly hybrid natural product synthesis, incorporating radical reactions, late-stage oxidation, and biological methods.