Convergent route

The first synthesis of a P-amyrin derivative was accomplished by a convergent route which depended on cation-olefin cyclization to form the critical central ring. The plan of synthesis was largely guided by the selection of SM goals for the A/B and E ring portions of the target. 

Fig. 12. Convergent routes to pseudorotaxane-terminated dendrimers with a metal complex at the cores and p CD at the periphery...

A highly convergent route for the synthesis of BILN 2061 has also been reported [112]. The synthesis is based on the assembly of four key fragments with an overall yield of 10-15% as shown in Scheme 2.1. The crucial step is a ring closing metathesis of an acyclic precursor. 

Originally, 1 was prepared by medicinal chemists from three key components, namely, a cyclopentanone moiety 2, a pyrazole moiety 3, and commercially available D-valine, as depicted in Scheme 2.1 [1], These synthetic disconnections provided an applicable and convergent route to 1, and consequently, were utilized in our strategy to develop an efficient and scalable synthesis of 1. 

In the course of our successful synthesis, we identified several limitations of our new method and associated strategy (1) the harsh conditions of the bicyclization reaction do not tolerate base-sensitive functionality such as vinyl halides (2) post-cyclization manipulations such as iododesilylation reactions are complicated by the sensitive/ reactive functionality of the products (a,p-unsaturated aldehyde, indoline, etc.) and (3) the incorporation of the required functionality into the Zincke aldehyde requires the synthesis of a complex tryptamine derivative, resulting in a lengthy, non-convergent route. In order to develop a concise route to strychnine, we would have to address each of these issues, and a straightforward solution to obviate all of these is described below. 

Insertions into acyclic alkenylzirconocene chlorides. A convergent route to functio-... 

The double iron-mediated arylamine cyclization provides a highly convergent route to indolo[2,3-fc]carbazole (Scheme 16). Double electrophilic substitution of m-phenylenediamine 34 by reaction with the complex salt 6a affords the diiron complex 35, which on oxidative cyclization using iodine in pyridine leads to indolo[2,3-b]carbazole 36 [98].Thus,ithasbeen demonstrated that the bidirectional annulation of two indole rings can be applied to the synthesis of indolocarbazoles. 

Recently, Price and and Osborne have developed a synthetically convergent route to produce libraries of Af-formylhydroxylamines that utilizes commercially available starting materials. In particularly, they have investigated the reaction of several electrophiles with the nitrogen atom of a solid-supported 0-protected A-formylhydroxylamine 221. 

Low 3delds indicate areas for improvements Convergent routes preferred, in principle If chiral, location of resolution step or integrity of induced stereocenters... 

The structure of the cytotoxic metabolite dendrodoine (81) from the tunicate Dendrodoa grossularia was determined by X-ray analysis [103] and it was later synthesised by a convergent route [104],... 

Pateamine (606), a potent cytotoxin containing a dilactone functionality, was isolated from a New Zealand species of Mycale and identified by analysis of spectral data [480]. Total synthesis of pateamine A (606) involved a (3-lactam based macrocyclisation [481,482], while another total synthesis of pateamine employed a concise and convergent route [483]. 

A synthesis of the Annonaceous acetogenin asimicin and a side-chain analogue has been achieved by a highly convergent route in which Grubbs cross-metathesis played a key role.98... 

The synthesis of a carbohydrate dendrimer consisting solely of mannopyrano-sides was accomplished via a convergent route [53]. 

Stoddart et al. developed a convergent route to polycationic dendrimers based on mesitylene units [65]. Positively charged dendrons obtained by the Menschut-kin reaction are attached as branching units around the l,3,5-tris(diethylamino-methyl)benzene core unit (3) (Fig. 4.36). (Anion) exchange of bromide with hex-afluorophosphate ions provides better solubility. 

Silane dendrimers with longer polysilane chains (e.g. with thirteen silicon atoms in the longest chain) were prepared by Lambert and Wu via a convergent route [73]. These molecules also assume an almost spherical shape. 

A convergent route to neolignans such as a potent and specific platelet-activating factor (PAF) antagonist, kadsurenone (18) and denudatin B (19), via a... 

One branch of the convergent route made the ketone 59 while the other made enantiomerically pure cis cyclopropane 60. These were combined to give the isocyanate 61 in two steps which was coupled to the amine 55 to give the urea 54. Though protection was still needed and the last step was still poor, the overall yield was 27%—a considerable improvement on 1%. The details of the chemistry are too advanced for this book but appear in Strategy and Control. 

Another important approach to the synthesis of helicenes is the convergent route based on energy-rich cis.cis-dienetriynes and their Ni(0)-catalyzed [2+2+2]-cycloisomerization, which was reported by Stara and coworkers [82, 83]. The potential of this methodology was demonstrated by the synthesis of functionalized... 

Racemic synthesis of double helical octaphenylene 67 was carried out via a convergent route. In the annelation step, the Cu(II)-mediated oxidative homocoupling of dilithiotetraphenylene, derived from the dibromotetraphenylene 66, gave octaphenylene 67 (Fig. 15.25) [107]. 

The Convergent Route to Globular Dendritic Macro molecules A Versatile Approach to Precisely Functionalized Three-Dimensional Polymers and Novel Block Copolymers [J. M. J. Frdchet, C. J. Hawker, K. L. Wooley, J. M. S.-Pure Appl. Chem. 1994, A31, 1627],... 

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