Lactone, 8-, precursor

Mass spectra of these alkaloids are almost identical with the mass spectra of their enol lactone precursors. It may be assumed that the molecular ions, recorded only in spectra of 104 and 106, can be easily dehydrated under electron impact (4,107,108). 

The photolysis of carboxylic acids and derivatives as lactones, esters and anhydrides can yield decarboxylated products 253>. This reaction has been utilized in the synthesis of a-lactones from cyclic diacyl peroxides 254) (2.34) and in the synthesis of [2,2]paracyclophane by bis-decarboxylation of a lactone precursor (2.35) 255). This latter product was also obtained by photoinduced desulfurization of the analogous cyclic sulfide in the presence of triethyl phosphite 256). 

Similarly, compound 73 was prepared from a persilylated D-galactono-1,4-lactone precursor in 60-80% yield (71). However, when unpurified Tebbe s reagent was employed, 1,4-lactones (for example 71a) gave a mixture of 72a and the product (74) of hydration of the double bond. The... 

In Yamada s retrosynthetic analysis (Scheme 11), elisabethin C (26) is traced back to lactone 64 which would be converted into 26 by deoxygenation and chain elongations. Key intermediate 64 could be obtained by a stereoselective Dieckmann cyclization. The required ester lactone precursor 65 would be accessible from 66 by a series of oxidation reactions. Further disconnection would lead to commercially available (+)-carvone (67). Stereoselective successive alkylation of 67 and reduction of the enone should deliver 66 [30]. 

Base for aldol coupling reactions, and tiie syntiiesis of lactone precursors and ketones. ... 

Synthesis from Chiral or Prochiral Lactone Precursors... 

In the synthesis of the compactin lactone precursor 76, an aldol—> 1,3-diol conversion was included in the usual sequence, and the required aldehyde function... 

Stereoselective routes to the lactone precursors of the 1-hydroxyethylene isosteres using a titanium-mediated condensation has been reported by both Shibuya and co-workers1 and DeCamp et al. 19 The former method (Scheme 9) features the reaction between (2S)-2-dibenzylamino aldehydes and optically active dichloroisopropoxytitanium ester homo-enolates to provide the desired lactone with high erythro selectivity. Then, the lactone is opened by treatment with an amine and trimethylaluminum to give the 1-hydroxyethylene isostere. The experimental details of DeCamp et al. s high yielding and stereoselective synthesis 19 of lactone 8 (Scheme 10) is discussed in Section 10.6.2.2. 

Kleinman and co-workers 20 synthesized a lactone precursor to the (2/ ,46, 56 )- -hydroxy-ethylene dipeptide stereoselectively in four steps using the lithium salt of ethyl propiolate as a homoenolate equivalent. As summarized in Scheme 11, addition of ethyl lithiopropiolate to a protected a-amino aldehyde affords hydroxy acetylenic esters as a mixture of dia-stereomers. Reduction of the acetylene group and subsequent lactonization gives a readily separable (4S)-lactone-enriched mixture. Direct alkylation with alkyl halide and lithium hexamethyldisilanazide yields the tram-lactone as the major stereoisomer. 

In several of the previously described methods the anion of the three-carbon fragments was added to an a-amino aldehyde to construct a C—C bond between the C3 and C4 atoms of the 1-hydroxyethylene isostere. However, Sakurai et al.[27l used an add chloride instead of an a-amino aldehyde. They synthesized 6-phthalimido-y-oxo esters by a palladium-catalyzed reaction between acid chlorides and organozinc reagents derived from p-iodo esters. Then, the oxo esters were converted into the y-lactone precursors. 

Ring-opening95 of tetrahydrofuran with TBDMS-Mn(CO)5, generated in situ from TBDMSOTf and NaMn(CO)5, proved a key step (equation 22) in the synthesis of spiroke-tal lactones, precursors of certain insect pheromones. 

Lactone precursor 173 was converted in 83% yield into enol ether 174 via Petasis methylation (Equation 9) <2004SL1434>. 

The redox-sensitive linker 1.34 (91), obtained in several steps from Merrifield resin and a lactone precursor, was charged with a N-protected aminoacid, treated with NBS to debenzylate and oxidize the linker to quinone, and submitted to SPS. The quinone linker was reductively activated to dihydroquinone with NaBH4 in THF/MeOH for 30 min at rt, then cleaved by treatment with anhydrous TBAF in THF for 20 h at rt to provide the free acidic peptide via intramolecular cyclization of the linker moiety. 

Prompted by the aim to synthesize for the first time the 7-OH derivatives TRIBOA and DHBOA a general procedure was established in which the crucial lactol unit is obtained by reduction of a lactone precursor (Fig. (10)). 

The asymmetric total synthesis of the putative structure of the cytotoxic diterpenoid (-)-sclerophytin A was realized via a Tebbe-Claisen rearrangement of a tricyclic lactone precursor in the laboratory of L.A. Paquette/ The tricyclic lactone was subjected to the Tebbe methylenation protocol to provide the allyl vinyl ether that was then heated to 130-140 °C in p-cymene to undergo the Claisen rearrangement in good yield. 

The first enantioselective formal total synthesis of paeonilactone A was reported by J.E. Backvall who used a palladium(ll)-catalyzed 1,4-oxylactonization of a conjugated diene as the key step. The lactonization precursor diene acid was obtained from an enantiopure dimethyl malonate derivative via sequential Krapcho decarboxylation and ester hydrolysis. 

The enantioselective total synthesis of the cyclooctanoid natural product (+)-epoxydictymene was accomplished in the laboratory of L.A. Paquette. The entire tricyclic framework was constructed by the application of a Claisen rerrangement via a chairlike transition state. The precursor for this / 3,37-sigmatropic rearrangement was obtained by treating a lactone precursor with the solution of the Tebbe reagent in the presence of pyridine. The corresponding enol ether was formed in almost quantitative yield, and immediately after isolation it was treated with triisobutylaluminum to effect the Claisen rearrangement. 

Masamune, in his studies of lactonization methodology, had previously converted 18 into cytochalasin B (20) as follows. The carboxylic acid moiety was converted to the thioester via the intermediate phosphoric anhydride. Exchange of the THP ethers for acetate groups then led to lactonization precursor... 

Same product distribution as for 7c, probably due to E/Z equilibration in the presence of the catalyst. b Overall yield from the lactonic precursor of7e. 

Union of ent-28 and 62 by bond formation between C9 and CIO was anticipated by the combined action of chromous chloride and nickcl(Il) chloride, the usual prescription for a successful NHK reaction. Advancement of NHK coupling product 63, representing atoms Cl-Cl 6 of polycavemoside A, to a suitable lactonization precursor 65 was projected to be a relatively straightforward operation. As it turned out, this aspect of the new plan would not be without difficulties vide infra). The terminal alkenes present at both C9 and C16 in this new series of... 

Kinsella, J. E., Patton, S., and Dimick, P. S. (1965). Chromatographic separation of lactone precursors and tentative identification of y-Iactones of 4-hydroxynananoic acids in butter-fat. J. Am. Oil Chem. Soc. 44, 202-205. 

CftHg02, Mr 112.13, mp. 134.5 °C, colorless needles, bp. 228 °C (decomp.) soluble in organic solvents and hot water. S. occurs in the seeds of the rowanberry (mountain ash, Sorbus aucuparia, Rosaceae) in the form of a lactone precursor, the so-called parasorbic acid [(65)-5,6-dihydro-6-methyl-2W-pyran-2-onej and is used for preserving foods. 

The strategy employed to discern the conformational preference of the less substituted oxocarbenium ions described above was not suitable for studying oxocarbenium ions with alkoxy groups at C2. When the lactone precursors 70 and 71 (Fig. 4.25) were subjected to alkylation conditions, the dioxocarbenium ion products 74 and 75 were not observed (Fig. 4.27). Instead, the reaction yielded a... 

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