5-lactone fragment

A similar cyclization is also used in the synthesis of a modified estron with ring A fused to a seven-membered lactone fragment <1999TL1771>. 

In spite of the academic significance of this synthesis, the industrial value of 8-lactone as a versatile starting material has remained low because of the few applications reported to date. Dinjus and coworkers [74] described the synthesis of polymers via the photoinitiated polyaddition of 8-lactone with various dithiols which displayed intact lactone fragments within the polymer backbone. However, the complicated synthesis and the formation of rather statistic polymers with hard-to-tune characteristics hindered their potential industrial applications. 

Biochemical methods in the enantioselective synthesis of natural products possessing oxirane and lactone fragments 92BSB393. 

As outlined in Table 6.16, the mass-selective detection of 2-methylbutanoic acid (esters) may interfere with the y-lacton fragment (m/e = 85) and/or analogous mass fragments from different classes of compounds. As to be seen from Table 6.16, even the selectivity of simultaneous multiple ion detection of 2-methylbutanoic acid (ester) fragments (m/e = 85, 88, 101) in the MIM-mode remains inconclusive, if the sample clean-up procedure was insufficient. 

INTERESTING SPIRO LACTONE FRAGMENT OF NEUROPEPTIDE Y (MILLIMETER-SIZE SINGLE-CHANNEL REACTOR)... 

Preparation of the lactone fragment started with a mixture of (2 ,45) and (25,4S)-4-methyl-2-phenylsulfenyl-y-butyrolactone (53) which was alkylated with ( )-l,9-diiodo-l-nonene. The corresponding iodo compound 100 so obtained was then coupled with the alkyne 99 through the efficient palladium catalyzed reaction (Pd(PPh3)4, Cul, Et3N, room temperature) in 86 % yield. Enyne reduction of 101 with Wilkinson s catalyst, then oxidation of the sulfide into sulfoxide and subsequent thermal elimination gave rise to the title compound 90. The synthesis was achieved in 20 steps and in 0.36 % yield. 

The chiral bicyclic lactam-lactone fragment of the antibiotic neooxazolomycin (378) has been synthesized using the MOM-protected methyl L-lactate analog 379 as the source of chirality [121] (Scheme 52). 

NH Deprotonations. During a modified Madelung indole synthesis, the convergent high-yielding condensation of the two main fragments of (—)-penitrem D, Ai-silylation (1.1 equiv BuLi) and lateral metalation (j-BuLi) of a complex o-toluidine substrate followed by condensation with a lactone fragment is carried out (eq 69). ... 

Ruthenium catalysts for hydroesterification are also known, but these catalysts typically operate by the addition of formates, rather than by the use of the combination of CO and alcohol. Nevertheless, some leading citations to this literature are provided here. In some cases, milder conditions have been developed with pyridylmethyl formates (Equation 17.36). These substrates were designed so that the pyridyl group would bind to the catalyst. -The synthesis of amides from olefins, CO, and amines is much less developed, and the most active catalyst for this process and for the addition of for-mamides to olefins is simply Ru3(C0)jj. Ruthenium-catalyzed hydroesterification with pyridylmethylformates has been used to prepare the lactone fragment of an HIV inte-grase inhibitor shown in Scheme 17.17. 

The unusual oleanic add "seco lycoside 24 has been isolated fix)m si beet it was postulated that the acetal linked (ficaibm c add lactone fragment is derived from a pentoade or fixmi a glucuronide with concomitant decartxn lation. ... 

Activated hydroxylamines react as able nucleophilic partners in the Mitsunobu reaction to provide key intermediates for further elaboration. The 5-lipooxygenase inhibitor CMI-977 was prepared using two sequential Mitsunobu reactions.After initial coupling of 4-fluorophenol to the lactone fragment, the homopropargyl alcohol was installed this intermediate, upon reaction with the phenoxycarbonyl activated hydroxylamine equivalent gave intermediate 188, which upon further reaction with ammonium hydroxide provided CMI-977 (189) in good yield. 

One of the pervasive problems in asymmetric synthesis has been the development of stereoselective acetate ester aldol reactions. Although a number of chiral auxiliaries perform superbly well in diastereoselective propionate aldol additions, these have, with rare exceptions, been unsuccessful in the corresponding additions of unsubstituted acetate-derived enolates [19, 63, 64). Braun s disclosure of a stereoselective acetate aldol addition reaction with 103 was an important milestone in the development of the field (Scheme 4.11) [63, 65]. The diol auxiliary can easily be prepared from mandelic acid esterification of the secondary alcohol is obsei ved, without interference from the tertiary counterpart. Its use has been showcased in a number of syntheses [53]. The high yield and diastereoselectivity generally obtained with 103 were highlighted by investigators at Merck in the construction of the chiral lactone fragment that is common in a number of HMG-CoA reductase inhibitors, such as compactin (105) [66]. 

Scheme 12.3 Enantioselective synthesis of the lactone fragment of tipranavir through a ring-opening/ring-closing metathesis (ROM/RCM) reaction. Ar = 2,4,6-Me3C6H2-...

Enantioselective Synthesis of the Lactone Fragment of Anti-HIV Agent Tipranivir... 

Unsaturated pyran 6 (Scheme 12.3) has been utilized (via 8) in the synthesis of the lactone fragment of tipranavir, a molecule discovered to possess potent activity against the HIV-protease enzyme [6]. Synthesis of enantiomericaUy enriched 7 (er = 95.5/4.5), a chiral product that would otherwise be difficult to access in the nonracemic form, is therefore achieved through a catalytic reaction of an easily available achiral substrate. Enantioselective preparation of 7 by an RCM process that involves the use of an achiral catalyst demands an effective protocol for preparation of the requisite O-substituted quaternary carbon stereogenic center. 

The 9 — 15 fragment was prepared by a similar route. Once again Sharpless kinetic resolution method was applied, but in the opposite sense, i.e., at 29% conversion a mixture of the racemic olefin educt with the virtually pure epoxide stereoisomer was obtained. On acid-catalysed epoxide opening and lactonization the stereocentre C-12 was inverted, and the pure dihydroxy lactone was isolated. This was methylated, protected as the acetonide, reduced to the lactol, protected by Wittig olefination and silylation, and finally ozonolysed to give the desired aldehyde. 

The (partial) description of the synthesis and coupling of the five fragments starts with the cyclohexyl moiety C —C. The first step involved the enantio- and diastereoselective harpless epoxidation of l,4-pentadien-3-ol described on p. 126f. The epoxide was converted in four steps to a d-vinyl d-lactone which gave a 3-cyclohexenecarboxylate via Ireland-CIaisen rearrangement (cf. p. 87). Uncatalysed hydroboration and oxidation (cf. p. 131) yielded the desired trans-2-methoxycyclohexanol which was protected as a silyl ether. The methyl car-... 

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