Ring dilactones

A synthesis of pyrenophorin using dithian shows how it works. The target 23 is a macrocyclic (16-membered ring) dilactone and disconnection of the ester linkages reveals two identical halves 24 pyrenophorin has C2 symmetry.7... 

Heat. When heated, succinic acid loses water and forms an internal anhydride with a stable ring stmcture. Dehydration starts at 170°C and becomes rapid at 190—210°C (25). Further heating of succinic anhydride causes decarboxylation and the formation of the dilactone of gamma ketopimelic acid (26) (eq. 1). The same reaction takes place at lower temperatures in the presence of alkaU. 

Previously, PLAs were obtained via condensation of lactic acid by heating and driving off water, which produced a gummy polymeric material of ill-dehned molecular weight and microstmcture [6]. Ring-opening polymerization (ROP) of dilactones, pioneered by Carothers in 1932 [7], was the hrst initiative for an... 

When heated with trimethyloxonium fluoroborate in 1,1-dichloroethane, dilactone 842 experiences cleavage of both lactone rings to give a mixture of diene diesters, catalytic reduction of which produced 853 Reductive methylation of 853 proceeded with installation of the methyl groups on the exterior face for obvious steric reasons. Acyloin condensation followed by ferric cloride oxidation furnished a-diketone 854 which proved to be highly responsive to photoexcitation. However, irradiation of 854 did not provide 855 as expected. Rather, a most unusual reaction pathway was followed to deliver diol 856. 

Fig. 33. Structure of pyridino dilactone (6) dihydrate 3) a as viewed perpendicular to the crown ring plane, b as seen in the plane of the crown...

On catalytic hydrogenation with Pt02 inumakilactone A (28) yielded the corresponding dihydro derivative 113 [40]. In contrast, the C ring double bond of inumakilactone B (31) was unaffected when this dilactone was catalytically hydrogenated with Pd-C [44]. 

New congeners of cytotoxic nor-diterpenoid dilactones in Podocarpus nagi three highly polar components with a-pyrone ring. Hayashi, Y. Yuki, Y. Matsumoto, T. Sakan, T. Tetrahedron Lett. 1977,34,2953-2956. 

Five- or six-membered lactones also are formed by internal esterification when either y- or 8-hydroxy acids are heated. Under similar conditions, /3-hydroxy acids are dehydrated to a,/3-unsaturated acids, whereas a-hydroxy acids undergo bimolecular esterification to substances with six-membered dilactone rings called lactides ... 

After these pioneering works, several reviews cover the enormous number of papers published in this field [3-7]. The synthesis of oxetanes can have a great importance in the development of compounds with relevant biological properties oxetane ring is present in the skeleton of taxol (1), an important drug used in the treatment of ovarian cancer [8] in merrilactone A (2), a new sesquiterpene dilactone with neurotrophic activity [9] and in several antiviral oxetanes, such as 3, 4, and 5, which have been described in literature (Scheme 3.2) [10-12],... 

It is remarkable that 1,3-cyclohexanediones with side chains containing seven, ten, and even twenty-one members are ring enlarged under basic anhydrous reaction conditions. The yields of the resulting 13-, 16-, and 27-membered ketone-lactones, are given in the following Table [104]. As expected, dimerized dilactones are side reaction products8). 

Barton oxidation was the key to form the 1,2-diketone 341 in surprisingly high yield, in order to close the five-membered ring (Scheme 38). The conditions chosen for the deprotection of the aldehyde, mercuric oxide and boron trifluoride etherate, at room temperature, immediately led to aldol 342. After protection of the newly formed secondary alcohol as a benzoate, the diketone was fragmented quantitatively with excess sodium hypochlorite. Cyclization of the generated diacid 343 to the desired dilactone 344 proved very difficult. After a variety of methods failed, the use of lead tetraacetate (203), precedented by work performed within the stmcmre determination of picrotoxinin (1), was spectacularly successful (204). In 99% yield, the simultaneous formation of both lactones was achieved. EIcb reaction with an excess of tertiary amine removed the benzoate of 344 and the double bond formed was epoxidized with peracid affording p-oxirane 104 stereoselectively. Treatment of... 

Two further cytotoxic nor-diterpenoid dilactones, (73) and (74), have been isolated " from Podocarpus nagi. Nagilactone F (75) has been synthesized from podocarpic acid. Two unusual diterpenoids, hispanonic acid (76) and his-paninic acid (77), both of which possess a seven-membered ring c, have been isolated from Ballota hispanica (Labiatae). Some naphthalenic nor-diterpenoids [e.g. (78)] with the cleistanthane skeleton have been isolated from Vellozia stipitata and V. declinans. 

During the total synthesis of the pentacyclic sesquiterpene dilactone (+)-merrilactone A by S.J. Danishefsky et al., a two-carbon unit was introduced at C9 by a Johnson-Claisen rearrangement. This high yielding transformation was carried out in the presence of catalytic 2,2-dimethyl propanoic acid at 135 °C using mesitylene as the solvent. A mixture of diastereomeric esters were formed, which were later hydrolyzed and subjected to iodolactonization to form the second lactone ring present in merrilactone A. The natural product was synthesized in 20 steps with an overall yield of 10.7%. 

S.J. Danishefsky and co-workers reported the total synthesis of pentacyclic sesquiterpene dilactone, merrilactone A. ° In their approach, they utilized Keck s radical allylation method to achieve the required chain extension. This sidechain was later used to construct one of the cyclopentane rings of the natural product. 

Macrodiolides. These dilactones of ring sizes 12 to 18 are obtained in fair to good yields. 

The phenyl coumaran, dihydro-dehydro-di- oeugenol (XXVIIa) and its methyl ether (XVIIb) reacted via cleavage of the B-ring, forming a dilactone (Figure... 

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