Fragmentation Strategies

The fragmentation strategy is based on a similar concept to traceless solid-phase chemistry, like retrocycloaddition cleavage, cycloelimination or cyclofragmentation. These are synthetically useful reactions with wide scope for the construction of rigid templates of different ring sizes. Up to now only one example for the attachment of heteroatoms via addition/elimination strategy has been developed, by Kurth et al. (Scheme 3.7) [188, 189]. 

The 9-membered ring present in quebrachamine has also been established using the fragmentation strategy [93],... 

Research by S. Arseniyadis and co-workers showed that the aldol-annelation-fragmentation strategy could be used for the synthesis of complex structures, which are precursors of a variety of taxoid natural products.This strategy allows the preparation of the twenty-carbon framework of taxanes from inexpensive and simple starting materials. 

The dodecapentanedioic acid moiety was prepared by a double Wittig type condensation of octatrienedial, followed by amidation of one of the carboxy groups with 2-amino-3-hydroxy-cyclopenten-2-one. Final condensation with the peptolide afforded enopeptin B (63) in 8% yield (Scheme 37). Other similar fragment strategies also gave poor yields. 

The "branched synthesis according to the fragment strategy 8) of Scheme 2 corresponds analogously to Pathway 2. 

The IMDA-Grob fragmentation strategy that starts with an allene cycloaddition reaction is illustrated in Scheme 43. The allene-furan cycloadduct was formed together with the other exoadduct which had the opposite configuration at the i-propyl group. Partial isomerization of the other product into the thermodynamic product shown and conversion into the 10-membered ketone constituted a formal synthesis of periplanone-B <88TL650l> since that ketone had been used in an... 

IV. SEVEN-MEMBERED RINGS FROM FRAGMENTATION STRATEGIES... 

Winkler employed a photochemical approach to the in-out tricyclic core of ingenol, beautifiilly illustrating the utility of a fragmentation strategy in complex molecule synthesis (Eq. 33). ... 

Paquette used a fragmentation strategy to elaborate the ring system of 18-oxo-3-virgene. Upon treatment with triethylamine in warm methanol, the starting material fragments to the seven-membered ring (Eq. 37). 

The Pj-22 isoforms were further purified by reverse phase HPLC (separation on the basis of hydrophobicity data not shown) and subjected to amino acid composition analysis. The data are summarized in Table 1. Knowing the relative amounts of each amino acid will define an enzymatic fragmentation strategy that will permit determination of the total Pj-22 sequence. 

The additional ring which arises from an intramolecular HDA reaction may enable us to synthesize various kinds of triquinanes or other polycyclic compounds based on our proposed cycloaddition-fragmentation strategy (Scheme 3). The decrease in entropy associated with tethering the two reactive components suggests that the reaction would be significantly more facile than the intermolecular reaction. This potential rate enhancement, however, is compromised by the dramatic decrease in rate associated with intermolecular cycloadditions with substituted norbor-nadienes (Section IID, Table 7). In fact, before our studies, only one example of an attempted intramolecular HDA reaction was reported in the literature (Eq. 15). Instead of undergoing a [2 + 2 + 2] cycloaddition, an alternative intramolecular ene reaction occurs. ... 

A one-pot synthesis of oxepanes via a cyclopropanol fragmentation strategy has been described. Using sequential addition of Al(OTf)3 and TiClq, only the cis-oxepane product was observed... 

New synthesis of naphthalide lignans, taiwanin C and justiddin E. Scheme 83 outiines a new synthesis of taiwanin C and justicidin E based on the cascade P-fragmentation strategy. 

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