Triene moiety

A distinguishing feature of the Nicolaou synthesis of rapamycin is the use of a palladium-mediated tandem inter-/intramolecular Stille coupling to construct rapamycin s 31-membered macrolide ring and conjugated triene moiety. This maneuver was unprecedented in the macrolide field,9 and it can be applied to a fully deprotected seco substrate (vide infra). 

Two methods have been developed to provide enantiomerically enriched cycloadducts using the chromium-mediated [6 + 2]- and [6 + 4]-cycloadditions one involving a chiral resolution and the other involving the attachment of a chiral auxiliary to the triene. The lipase resolution method provides access to either enantiomer of the chromium complex, albeit with moderate enantiomeric excesses (Scheme 34).119 The [6 + 4]- and [6 + 2]-reactions of chiral substrates such as 116 which are available by the attachment of a removable chiral auxiliary (R ) to the triene moiety are highly diastereoselective (Equation (17)).120... 

One reason for an otherwise apparently excessive interest in Co(trien)X2+ systems is the use of ds-Co(OH)(trien)(OH2)2+ in the hydrolysis of amino acid esters, amino acid amides and peptides785 to form cis-px- and cis-/J2-Co(trien)(aa)2+ (aa = amino acid) complexes.16 In principle, a peptide could be degraded in a stepwise manner and each amino acid residue successively characterized. By the introduction of a chiral center into the backbone of the trien moiety, it was hoped to make such reactions stereoselective. Consequently, while fully A-alkylated trien systems have been widely investigated for M11 central ions, the C-alkylated trien systems have been almost exclusively the reserve of the Co111 chemist (Table 11). 

C=C triple bond and the Zr/Zn exchange reaction H — G. The electrophilic reaction partners are the stereouniform haloalkenes C and D. Three C-ZnHal- and three C-Hal bonds are reacted with each other by pairs and always with complete retention of configuration (A+C-)E, B + D- F and G l E —> I). This results in a /ra/j.v-con figuration of all C=C double bonds of the central triene moiety of the target molecule. 

The first report of a topochemical 1,6-polymerization of a conjugated triene was recently described by Lauher and co-workers [39]. In particular, the double ester of l,8-dihydroxy-2,4,6-octatriene and nicotinic acid (Scheme 2.3.5) was found to adopt a solid-state packing arrangement conducive for the 1,6-polymerization. Specifically, the molecules were oriented at a repeat distance of 7.2 A (Fig. 2.3.3(a)). Although the separation between terminal carbon atoms of adjacent triene moieties was somewhat large (4.09 A), the solid underwent a SCSC topochemical... 

In a recent elegant synthetic application of this methodology, Vande-walle and co-workers have prepared some vitamin D3 derivatives.60 Scheme 6-VI shows a synthesis of 12-hydroxy vitamin D3 from 7-dehy-drocholesterol. The key feature of this route is the protection of the sensitive triene moiety as its Diels-Alder adduct with jV-phenyltriazoline-3,5-dione. 

Ascidiatrienolide A (85) and neodidemnilactone (88) proved to be geometrical isomers of the triene moiety with the same absolute configurations of the stereocenters on the lactone ring part. 

Rapamycin (sirolimus 2), isolated from Streptomyces hygroscopicus, is a highly functionalized 31-membered macrolide that exhibits potent antibiotic, cytotoxic, and immunosuppressive activity. FK506 (1) and rapamycin (2) are the structurally related macrolides (Fig. 1) thus, rapamycin possesses an a,p-diketoamide hemi-ketal system, a pipecolic acid moiety, 1,2,4-trisubstituted cyclohexane, and trisub-stituted tetrahydropyran rings, which are similar to those of FK506. In addition to these units, rapamycin (2) includes an ( , , )-triene moiety, two stereochemically complex aldol units, and 15 chiral centers beyond those found in FK506. 

Coordinated cycloheptatrienes show a considerably larger upheld shift on complexation ( 40 ppm) relative to analogous A -arene derivatives ( 25 ppm) (147). A possible explanation may lie in the greater strength of the triene-metal bond. The preferential coordination of the triene moiety in 1-phenylcycloheptatriene complexes is consistent with this view. Fluxional properties of A -cycloheptratriene and A -cyclooctatriene complexes are dis-... 

The acute toxicity of trienomycin A was very low at >400 mg/kg [14,18].The cytotoxicity of trienomycin A was lowered by reducing the triene moiety and/or by omitting the acyl alanyl moiety of the side chain [19]. 

The second approach involved initially applying the aminolysis reaction with an excess of furfurylamine (as described above) to TO, which gave three fatty-acid amides with the triene moiety and a furan end group, and then polymerising them with the same selection of BM used in the first approach [13]. These linear polycondensations involved, therefore, two distinct DA couplings one between a maleimide function and a furan heterocycle, and the other between a maleimide function and the triene moiety (Scheme 7.8b). 

However, in the latter case, a cationic rhodium(I) complex had to be added to catalyze the intramolecular Diels-Alder reaction with the triene moiety to give a diene, ready for an intermolecular [4 -I- 2] cycloaddition. Strictly speaking, this case is definitely a borderline one with respect to the rigorous definition given in the introduction. 

The [Co(en)2] and [Co(trien)] moieties are chiral and some specificity is induced when optically active cobalt(III) units are employed. 

Danishefsky and co-workers reported a total synthesis of antibiotic t//-indolizomycin 121. In which Julia olefination was successful employed to prepare the triene moiety. The intermediate 119, prepared by addition of 118 to aldehyde 117, was reduced to 120 by using 5% Na(Hg). 

In their efforts to prepare a [D4]-labeled p4t-neuroprostane, the Galano group carried out partial reduction of the skipped diyne substrate in order to access the Z,Z,Z-triene moiety of the final product (Fig. 12) [34]. While Lindlar s catalyst provided a mixture of mono-reduction of the less hindered alkyne (with the ethyl substituent), the desired triene as well as over-reduced diene product, P-2 nickel yielded a much cleaner conversion to the desired product with 98% purity. The product was then transformed into the target molecule by a sequence of TBAF deprotection of the TBS ether and saponification. 

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