Convergent block synthesis

Despite the availability of more advanced techniques, the convergent block synthesis is still widely employed, and the following is only a short list of recent examples.73-90... 

A dendrimer-based approach for the design of globular protein mimics using glutamic (Glu) and aspartic (Asp) acids as building blocks has been developed [151]. The preassembled Glu/Asp dendrones were attached to a 1,3-bifunctional adamantyl based on a convergent dendrimer synthesis strategy (see Fig. 28). 

Another highly versatile building block derived from diacetone-glucose 54 is the 1,2-acetonide of 3-C-methyl-a-D-allose in its furanoid form 57, which has been utilized as the key compound in a convergent total synthesis of ACRL Toxin I (63). Its elaboration from 54 starts with a pyridinium dichromate / acetic anhydride oxidation (64), is followed by carbonyl olefination of the respective 3-ulose with methyl (triphenyl)phosphonium bromide and hydrogenation (— 55 56), and is completed by acid cleavage of the 5,6-isopropylidene group. This four-step process 54 -> 57, upon optimization of reaction conditions and workup procedure, allows an overall yield of 58 % (63), as compared to the 22 % obtained previously (65). 

The utilization of the furanoid 3-C-methyl-D-allose building blocks 57 and 60 for a convergent total synthesis of ACRL Toxin I in the form of its stable 3-0-methyl ether (63) involved their conversion into enantiomerically uniform connective segments. The key feature of the retrosynthesis was the expectation... 

The examples discussed in this paper demonstrate that Pd-catalyzed coupling reactions can be successfully utilized in the convergent (modular) synthesis of vitamin D-active compounds. The new synthetic routes open an efficient and highly selective access to a variety of vitamin D analogs. While reliable methods exist today for the construction of the triene system and for the synthesis of the ring A precursors, the search for efficient total synthetic approaches to the CD building blocks still remain a challenging task for the future. 

Included are two examples of the two- and three-step sequential oligosaccharide assembly to illustrate Approach A. The first synthesis makes use of trichloroacetimidate 239, which is selectively activated over the thioglycoside acceptor 240 with TMSOTf (Scheme 49). The SPh moiety of the resulting tetrasaccharide is then activated over the added glycosyl acceptor 241 by addition of NIS and TfOH to provide hexasaccharide 242 in 50% yield over two steps.100 This approach combines advantages of the selective activation, convergent block strategy, and one-pot synthesis. 

In spite of the poor selectivity in two of the coupling reactions, the overall yield of the mannohexaose 321 from the block synthesis was higher than that achieved previously in the linear synthesis, thereby clearly highlighting the well-known advantages of convergent syntheses. 

In 1998 [102], Kitahara et al. reported also a convergent total synthesis of (-)-pironetin by using three chiral buiding blocks the (lS,5S,6R)-5-hydroxy-bicyclo[4.1.0]heptan-2-one, a dithiane and an epoxide. As in the previous synthesis, the nucleophilic addition of the dithiane to the epoxide... 

Deoxyerythronolide B (18 Scheme 2), a monocyclic 14-membered lactone containing 10 asymmetric centers, is produced by blocked mutants of Streptomyces erthreus, and is a common biosynthetic precursor leading to all the erythromycins. A convergent total synthesis of 18 requires the appropriate chiral left- and right-hand fragments, which provides an excellent opportunity for these chiral boron enolates to demonstrate their versatility. 

A convergent total synthesis of amphotericin B (517), with a jS-linked mycosamine at the C-19 hydroxyl position, a clinically useful antifungal agent isolated from Streptomyces nodosus, and its aglycon, amphoteronolide B (518), relies upon the stereocontrolled construction of enantiomerically pure (homochiral) structural units. Retrosynthetic analysis of 517 uncovers certain stereochemical features that allow construction of two of the essential chiral building blocks from 514, the chiral antipode of 503 and readily available from lb, by utilizing similar reaction conditions to those available for the synthesis of 503. Thus, chiral... 

In 2002, Lett et al. published a convergent stereospecific synthesis of the resorcylic macolactone LL-Zl 640-2 (567) (Scheme 9.13) and hence hypothemycin (481) 382, 383). They started with the preparation of the three building blocks, 551, 555 (Scheme 9.11), and 564 (Scheme 9.12). Methyl ester 551 was produced from 4-methoxysalicylic acid (549) in four steps. Reaction of alkyne 552 with enantiopure (/ )-propylene oxide 490 afforded chiral alkyne 553, which then was converted into (Z)-vinyl iodide 555. 

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