Dienes macrocyclic compounds

Attempts to synthesise L183 in the absence of metal ions were unsuccessful. This may be due to low stability of the azomethine bonds of the cis diene macrocyclic compound to acid hydrolysis. This assumption is proved by the conversion of LI83 into L185 under the action of perchloric acid [227, 228],... 

Since then, the metathesis reaction has been extended to other types of alkenes, viz. substituted alkenes, dienes and polyenes, and to alkynes. Of special interest is the metathesis of cycloalkenes. This gives rise to a ring enlargement resulting in macrocyclic compounds and eventually poly-... 

The Wittig reaction was employed to fuse diene 49 and aldehyde 50, in the final stages of the stereoselective synthesis of epothilone B, a macrocyclic compound with potential antifungal properties (equation 31)49. 

Remarkably, this precatalyst could also be successfully applied in the RCM of several representative diene substrates, allowing the synthesis of essentially all ring sizes greater than four, including mono- and bicyclic compounds, in good to excellent yields, as well as a set of uncommon macrocyclic compounds (representative examples are shown in Scheme 37) [140, 141, 143, 298-300]. 

For tabulation, the non-macrocyclic trichothecenes have been subdivided into 12,13-epoxytrichothec-9-enes (103, 77%) (Table 1), 12,13-epoxytrichothec-9-en-8-ones (23, 17%) (Table 2), trichothec-9,12-dienes (5, 4%) (Table 3), and miscellaneous (2) (Table 4). Thus, all but five of the non-macrocyclic trichothecenes have the 12,13-epoxide group. The pair of diastereoisomers in Table 4 have a 9,10-epoxide and are the only non-macrocyclic compounds not to have the 9(10)-ene implicit in the name trichothecene. 

The last group of trichothecenes are the trichoverroids which appear in Table VIII. These seco macrocyclic trichothecenes have either partial or complete carbon chains at C-4 and C-15 characteristic of the macrocyclic compounds, but lack the requisite ring-forming bond. The first of these, trichodermadiene (72), was reported by Jarvis and co-workers in 1980 (77). In this compound a diene fragment is affixed to C-4 in a manner reminiscent of the macrocycles, but the C-15 hydroxyl group remains unesterified. Subsequently, Jarvis 78, 83, 86) discovered other such seco compounds which possess the complete carbon chains of the macrocyclic trichothecenes. Evidence has been presented suggesting that the trichoverroids are intermediates in the biosynthesis of the macrocycles 78). 

Related to the crown ethers are compounds, such as hexamethyl-[14]-4,ll-diene (6), which differ by the replacement of one or more of the oxygen atoms by other kinds of donor atoms, particularly N or S. MacrocycHc amine and thioether compounds have been synthesized. Compounds having more than one kind of heteroatom in the ring are called mixed-donor macrocycles. The naturally occurring metaboUtes nonactin [6833-84-7] and monactin [7182-54-9] have both ether and ester groups incorporated in the macrocyclic stmcture. 

Diene 265, substituted by a bulky silyl ether to prevent cycloaddition before the metathesis process, produced in the presence of catalyst C the undesired furanophane 266 with a (Z) double bond as the sole reaction product in high yield. The same compound was obtained with Schrock s molybdenum catalyst B, while first-generation catalyst A led even under very high dilution only to an isomeric mixture of dimerized products. The (Z)-configured furanophane 266 after desilylation did not, in accordance with earlier observations, produce any TADA product. On the other hand, dienone 267 furnished the desired macrocycle (E)-268, though as minor component in a 2 1 isomeric mixture with (Z)-268. Alcohol 269 derived from E-268 then underwent the projected TADA reaction selectively to produce cycloadduct 270 (70% conversion) in a reversible process after 3 days. The final Lewis acid-mediated conversion to 272 however did not occur, delivering anhydrochatancin 271 instead. 

Similarly, the DA reaction of o-benzoquinodimethane with the hexaphyrin 16, followed by treatment with DDQ, gave rise to the naphthohexaphyrin 17 <05AC(E)932>. This result revealed that the first addition of the diene took place selectively at the inner inverted beta-pyrrolic double bond, suggesting that this double bond is the most reactive position of the macrocycle. In minor amount the reaction also gave rise to a bisnaphthohexaphyrin. Curiously, this compound resulted from the selective addition of a second o-benzoquinodimethane species to an outer befa-pyrrolic double bond of the naphthohexaphyrin 17, and is in agreement with the theoretical calculations that predicted that the second cycloaddition could not occur at the other side of the inner double bond of 17. 

The first efficient application of a well-defined ruthenium indenylidene complex in metathesis was described in 1999 by Frirstner for the total synthesis of a cyclic prodigiosin derivative, a potential lead compound for the development of immunosuppressive agents. The RCM using the ruthenium indenylidene complex DC (10 mol%) as precatalyst leads to the transformation of the N-protonated diene into the desired macrocycle in 65% yield (Equation 8.8) [43]. 

Dienes are cyclized by intramolecular metathesis. In particular, cyclic alkenes 43 and ethylene are formed by the ring-closing metathesis of the a,co-diene 46. This is the reverse reaction of ethenolysis. Alkene metathesis is reversible, and usually an equilibrium mixture of alkenes is formed. However, the metathesis of a,co-dienes 46 generates ethylene as one product, which can be removed easily from reaction mixtures to afford cyclic compounds 43 nearly quantitatively. This is a most useful reaction, because from not only five to eight membered rings, but also macrocycles can be prepared by RCM under high-dilution conditions. However, it should be noted that RCM is an intramolecular reaction and competitive with acyclic diene metathesis polymerization (ADMET), which is intermolecular to form the polymer 47. In addition, the polymer 47 may be formed by ROMP of the cyclic compounds 43. 

The inherent flexibility of the RCM approach was illustrated by the synthesis of several analogues differing from tricolorin A in their ring size and hence lipophilicity (Scheme 8). For this purpose, diol 55a was reacted with unsaturated acid derivatives other than 6-heptenoic acid and the dienes 58 and 59 thus formed were processed as described above. This allowed us to access compound 60 missing two of the CH2-groups in the macrocyclic loop of... 

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