Novel Approaches to Antitumor and Antiviral Agents

抗肿瘤抗病毒药物的治疗重要性需要不断努力开发新的方法来确定更好的合成策略。选择具有这种生物活性的化合物作为目标，该项目开发了新的化学原理，这些原理可能演变成创造这种分子结构的前所未有的策略。不对称烯丙基酰化涉及钯和环氧化物或相关的环状碳酸盐可能提供了一种简单的策略，以形成指向丝裂霉素型结构的构建块。诱导前手性亲核试剂的不对称是催化不对称事件中手性识别最具挑战性的任务之一。初步的成功刺激了它的探索。应用的广度是巨大的，从生物碱，如临床上重要的长春花生物碱到大环，如peloruside A.一个新的版本结合了不对称诱导原亲核试剂和一类新的亲电试剂，烯，来创建一个非常短的合成不寻常的酰胺类型，如spirotyprostatin。由不对称烯丙基烷基化引发的一系列串联立体特异性过程调用环二酮，创造了一种概念上前所未有的新型萜烯，如特培他星。新发明的钌催化反应将在各种聚酮的合成中进行测试和探索，如月桂烷和月桂烷。通过钌催化的环异构化反应或适当的双炔加水反应，提出了一种通过原子经济加成构建简单多官能团环的全新概念。最令人兴奋的目标层出不穷。在许多项目中，氢基硅烷化的完全前所未有的选择性有助于简化合成设计，包括丝裂霉素模拟物和ptsloruside a .一个直接的不对称醛醇方案提供了许多结构类型的途径，包括leustroducsin， peloruside a和apicularen a .通过加速获得非常多样化的结构类型阵列，发现新的治疗药物的最佳机会出现。

The therapeutic importance of antitumor antiviral agents requires a continued effort to develop new methodology to define better synthetic strategies. Choosing classes of compounds known for this type of biological activity as targets, this project develops new chemical principles that may evolve into unprecedented strategies for creating such molecular architectures. Asymmetric allylic akylation involving palladium and epoxides or related cyclic carbonates may provide a simple strategy to form a building block directed toward mitomycin - type structures. Inducing asymmetry at a prochiral nucleophile represents one of the most challenging tasks ever for chiral recognition in a catalytic asymmetric event. Preliminary successes stimulates its exploration. The breadth of applications is huge - ranging from alkaloids like the clinically important vinca alkaloids to macrocycles like peloruside A. A novel version combines asymmetric induction of a pronucleophile with a new class of pro-electrophiles, allenes, to create an extremely short synthesis of unusual amide types such as spirotyprostatin. A series of tandem stereospecific processes initiated by the asymmetric allylic alkylation invoking cyclic diketones creates a conceptually unprecedented approach to novel terpenes like terpestacin. New Ru catalyzed reactions being invented will be tested and explored in the synthesis of diverse polyketides like the laulimalides and pelorusides. A totally new concept for simple polyfunctional ring construction by atom economic additions is visualized via Ru catalyzed cycloisomerization or water addition to suitable diynes. Numerous targets emerge with the most exciting. In a number of projects, totally unprecedented selectivities in hdyrosilylation helps simplify the synthetic design including the mitomycin mimic and ptsloruside A. A direct asymmetric aldol protocol provides access to numerous structural types represented by leustroducsin, peloruside A, and apicularen A. By expediting access to very diverse arrays of structural types, the best opportunities to discover new therapeutic agents arise.