Enantioselective Total Synthesis of Marine Alkaloids Stellettamides

海洋生物碱司太酰胺的对映选择性全合成

• 批准号: 13672235
• 负责人: YAMAZAK Inaoki
• 金额: $ 1.86万
• 依托单位: Tokyo University of Pharmacy and Life Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672235/
• 关键词: (+)-stellettamide A; (-)-stellettamide B; (1S,4S,8aR)-stellettamide C; marine sponge; calmodulin inhibitor; antifungal activity; ( R )-2-(1-aminoethyl)phenol; nitrogen containing natural products; 海洋アルカロイド; 全合成; 四級窒素; 不斉アリル化; RNA切断活性; 抗菌作用

Stellettamid A was first isolated by Fustian in 1990 from a marine sponge of the genus Stelletta collected in Shikinejima of Japan as the first representive of an indolizidine class of marine alkaloids. Subsequently, Shin reported the isolation of the closely related alkaloid stellettamide B from a Korean specimen of Stelletta. Very recently, another alkaloid, stellettamide C was isolated from the Japanese sponge. Stellettamides A-C comprise a common indolizidine skeleton, containing a quaternary nitrogen atom and a variation of the unsaturated side chain, which are connected via an amide linkage. The present investigations were aimed at the first asymmetric total synthesis of stellettamides A, B, and C in an enatiomerically pure form utilizing asymmetric allylation of the chiral N-acyl-N, O-acetalThe tricyclic N-acyl-N, O-acetal incorporating ( R )-2-(1-aminoethyl)phenol as a chiral auxiliary underwent TiCl_4-mediated allylation to give the chiral allylpiperidinone with retention of configuration in high yield and diastereoselectivity. The first total synthesis of (+)-stellettamide A has been achieved by a sequence based on amide coupling of the chiral 1-(aminomethyl)indolizidine fragment, prepared from the (6R)-allylpiperidinone, with the chiral trienoic acid fragment. By employing the same methodology, the syntheses of (-)-stellettamide B and (1S,4S,8aR)-stellettamide C have been achieved. The synthesis of stelletamide B led to revision of the published relative stereochemistry of the natural product and established its absolute stereochemistry to be 1S,4S,8aR,6"R

Stellettamid A于1990年首次由Fustian从日本敷根岛采集的Stelletta属海绵中分离出来，是吲哚里西啶类海洋生物碱的第一个代表。随后，Shin报道了从韩国的Stelletta标本中分离出了密切相关的生物碱Stelvanamide B。最近，从日本海绵中分离出另一种生物碱，stelvanamide C。星形酰胺A-C包含共同的吲哚里西啶骨架，其含有季氮原子和不饱和侧链的变体，它们通过酰胺键连接。本研究旨在利用手性N-酰基-N，O-缩醛的不对称烯丙基化反应首次不对称全合成对映体纯形式的星草酰胺A，B和C。掺入（R）-2-的O-缩醛1-氨基乙基苯酚作为手性助剂，介导的烯丙基化反应，以高产率和非对映选择性得到手性烯丙基哌啶酮。首次全合成了（+）-stelvanamide A，通过基于由（6 R）-烯丙基哌啶酮制备的手性1-（氨甲基）吲嗪片段与手性三烯酸片段的酰胺偶联的序列实现。采用同样的方法，合成了（-）-司他林酰胺B和（1 S，4S，8aR）-司他林酰胺C。星草酰胺B的合成对已发表的天然产物的相对立体化学进行了修正，确定其绝对立体化学为1 S，4S，8aR，6“R

项目成果

Naoki Yamazaki, Masakazu, Atobe, Chihiro Kibayashi: "Nucleophilic Addition of Methyllithium to Chiral Oxime Ethers : Asymmetric Preparation of 1-(Aryl)ethylamines and Application to a Synthesis of Calcimimetics (+)-NPS R-568 and Its Thio Analogue"Tetrahed

Naoki Yamazaki、Masakazu、Atobe、Chihiro Kibayashi：“甲基锂与手性肟醚的亲核加成：1-(芳基)乙胺的不对称制备及其在拟钙剂 ( )-NPS R-568 及其硫代类似物合成中的应用”Tetrahed

Naoki Yamazaki, Masakazu, Atobe, Chihiro Kibayashi: "Nucleophilic Addition of Methyllithium to Chiral Oxime Ethers: Asymmetric Preparation of 1-(Aryl)ethylamines and Application to a Synthesis of Calcimimetics (+)-NPS R-568 and Its Thio Analogue"Tetrahedr

Naoki Yamazaki、Masakazu、Atobe、Chihiro Kibayashi：“甲基锂与手性肟醚的亲核加成：1-(芳基)乙胺的不对称制备及其在拟钙剂 ( )-NPS R-568 及其硫代类似物合成中的应用”四面体

Naoki Yamazaki, Wataru Dokoshi, Chihiro Kibayashi: "Total Synthesis of (-)-Stellettamide B and Determination of Its Absolute Stereochemistry"Organic Letters, 3. 3. 193-196 (2001)

Naoki Yamazaki、Wataru Dokoshi、Chihiro Kibayashi：“(-)-Stellettamide B 的全合成及其绝对立体化学的测定”Organic Letters，3. 3. 193-196 (2001)

Toshimasa Itoh, Naoki Yamazaki, Chihiro Kibayashi: "Asymmetric Synthesis of (-)-Adaline"Organic Letters. 4・15. 2469-2472 (2002)

Toshimasa Itoh、Naoki Yamazaki、Chihiro Kibayashi：“(-)-Adaline 的不对称合成”有机字母 4・15 (2002)。