Synthesis of Petrosins C and D

Petrosins C and D (5 and 6), diastereomers of the known natural products petrosin (1), petrosin A (2), and petrosin B (3), have been prepared. The synthetic route involved initial creation of a 16-membered bis-pyridine intermediate, exemplified by compounds 7, 28, and 52. Several different methods for formation of the macrocycle were evaluated, and the most efficient (Schemes 7−9) involved use of Z double bonds in the six-carbon chains linking the two pyridine rings. This approach permitted the two pyridine subunits (37 and 39) to be joined by alkylation of a lithiated α-methylpyridine with an allylic chloride (e.g., 37 + 39 → 40 and 49 → 45). Bisannulation of compounds 7 and 28 was complicated by a surprising lack of acidity of the α-pyridyl methylene groups. Eventually, this problem was solved by stepwise introduction of two allyl groups, using the more acidic sulfone for introduction of the first (e.g., 52 → 53) and direct allylation to introduce the second (e.g., 54 → 55 + 56). The bisannulation was c...

已制备出岩芹素C和D（5和6），它们是已知天然产物岩芹素（1）、岩芹素A（2）和岩芹素B（3）的非对映异构体。合成路线包括首先制备一个16元双吡啶中间体，以化合物7、28和52为例。对几种形成大环的不同方法进行了评估，最有效的方法（方案7 - 9）涉及在连接两个吡啶环的六碳链中使用Z型双键。这种方法使得两个吡啶亚基（37和39）能够通过锂化的α - 甲基吡啶与烯丙基氯的烷基化反应连接起来（例如，37 + 39 → 40以及49 → 45）。化合物7和28的双环化由于α - 吡啶基亚甲基令人惊讶地缺乏酸性而变得复杂。最终，通过逐步引入两个烯丙基解决了这个问题，利用酸性更强的砜引入第一个烯丙基（例如，52 → 53），并通过直接烯丙基化引入第二个烯丙基（例如，54 → 55 + 56）。双环化是……