Protecting moieties benzyl, substituted

There are dozens of linkers available for synthesis, and nearly all of them, once acylated by a protected amino acid, provide a benzyl ester or a benzyl amide that has been sensitized to cleavage by acid by the presence of electron-donating moieties such as alkoxy, phenyl, or substituted phenyl. There are cases in which a peptide chain is bound to a support through two different linkers in series. This allows for versatility in synthesis. The distinction between designation of a moiety affixed to a support as a handle or linker is sometimes arbitrary. 

The normal mode of reaction of cycloproparenes with electrophiles involves opening of the three-membered ring and leads to benzylic derivatives (see Section 3.B.3.). The bis(triiso-propylsilyl) group offers efficient protection of the cyclopropene moiety, so that electrophilic attack of the protected benzocyclopropene occurs at the aromatic ring. Reaction of 1,1-bis(triisopropylsilyl)benzocyclopropene with 67% nitric acid gave the 3-nitro derivative 1 in 58% yield. Electrophilic attack on the cycloproparene occurs at C3 and this is consistent with theoretical calculations. A variety of substituted derivatives of benzocyclopropene are available from the nitro compound (see Section 3.5.). 

More recently, the same catalyst was used to produce cyclic amines with retention of stereochemistry from a simple linear aliphatic azide [53]. Treatment of a substituted aliphatic azide by complex 66 afforded the cyclized compound 75, by insertion of the nitrene moiety in allylic, benzylic, and even in the less reactive tertiary C—H bonds. The catalyst is inhibited by coordination of the product to the metal center. However, that can be avoided by using an in situ protecting agent (Boep is preferred over Fmoc-OSuc which leads to catalyst decomposition). 

Danishefsky s synthesis (Scheme 4) [7] started from the readily available Wieland-Mie-scher ketone (19) which, by a series of mainly protection and oxidation reactions, was transformed to the fully functionalized C ring precursor 21. The oxetane moiety was introduced very early on in the synthesis, from a corresponding triol, again by nucleophilic substitution at C5. Noteworthy is the selective protection or modification of primary versus secondary versus tertiary hydroxy groups for this purpose. The benzyl protected enolized form 20 then could be oxidized, cleaved oxidatively and processed to compound 21 which, apart from complete C/D rings, possesses the necessary handles (C2 and C9/10) to bind to the A ring precursor 22 and thus form the B ring. 

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