Mixed carbonates

Work at Rhc ne-Poulenc has involved a different approach to retinal and is based on the paHadium-cataly2ed rearrangement of the mixed carbonate (41) to the aHenyl enal (42). Isomerization of the aHene (42) to the polyene (43) completes the constmction of the carbon framework. Acid-catalyzed isomerization yields retinal (5). A decided advantage of this route is that no by-products such as triphenylphosphine oxide or sodium phenylsulfinate are formed. However, significant yield improvements would be necessary for this process to compete with the current commercial syntheses (25—27) (Fig. 9). 

The r-Bumeoc adduct is prepared from the acid fluoride or the mixed carbonate in dioxane, H2O, NaOH. 

Several protective groups have been prepared that rely on a /3-elimination to effect cleavage. Often the protective group must first be activated to increase the acidity of the jS-hydrogen. In general the derivatives are prepared by standard procedures, from either the chloroformate or mixed carbonate. 

The following carbamates can be cleaved by photolysis. They can be prepared from either the chlorbformate or the mixed carbonate. 

Condensation of prednisone, 40 with tetraethyl orthocarbonate leads to the cyelie ortho-carbonate 41 liydrolysis proceeds by protonation on the most accessible ether oxygen (that on carbon 21) to give the 17 mixed carbonate ester 42. Acylation with propionyl chloride proceeds on the remaining hydroxyl group to afford prednicarbate (43) [10],... 

Saponification of the acetate, followed by conversion of the newly formed primary hydroxyl group to a mixed carbonate in the conventional way with methyl chloroformate and pyridine, provides intermediate 34. At this juncture, it is instructive to draw attention to the fact that the oxygen atom at C-15 and the mixed carbonate in... 

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

The decomposition of MgC03 (magnesite) is an interface process [734] between 813—873 K and E = 150 kJ mole-1. In the presence of C02, E was increased to 234 kJ mole-1 but was reduced slightly on the addition of ZnO or NiO. Admixture with CaO reduced the value of E to 54 kJ mole-1. This is a surprising result since the value of E for decomposition [734,753] of the mixed carbonate (Ca, Mg)C03, dolomite, is 220 kJ mole-1, larger than the value for each constituent. The influence of PCOz and of alkali metals on MgC03 decomposition has been the subject of a DTA study [404]. 

F.20 Dolomite is a mixed carbonate of calcium and magnesium. Calcium and magnesium carbonates both decompose on heating to produce the metal oxides (MgO and CaO) and carbon dioxide (C02). If 4.84 g of residue consisting of MgO and CaO remains when 9.66 g of dolomite is heated until decomposition is complete, what percentage by mass of the original sample was MgC03 ... 

A reaction of the same nature was probably responsible for a detonation that took place one hour after mixing carbon tetrachloride with tetraethylene pen-tamine. This reaction also occurs with monoamines, but it is not thought to be dangerous. 

The t-butoxycarbonyl (rBoc) group is another valuable amino-protecting group. The removal in this case is done with an acid such as trifluoroacetic acid or /Moluenesulfonic acid.218 r-Butoxycarbonyl groups are introduced by reaction of amines with f-butoxypyrocarbonate or a mixed carbonate-imidate ester known as BOC-ON. 219... 

By adding one equivalent of alcohol to CDI at room temperature with or without base it is possible to isolate the imidazole-iV-carboxylate, which then reacts with a second mole of ROH to yield the carbonate. As in the case of alcoholysis of imidazolides, the reaction can be accelerated so effectively with catalytic amounts of NaOC2H5 or ImNa that it takes place in most cases exothermically, even at room temperature. However, tert-butyl alcohol, even when in excess, affords with CDI and base catalysis at room temperature only the imidazole-N-tert-butylcarboxylate, obviously for steric reasons. At higher temperature the carbonic ester is formed. Mixed carbonates such as ethyl benzyl carbonate or ethyl terf-butyl carbonate can be prepared with two different alcohols added sequentially.C9],[229]... 

Carbon limiting is also used to encourage enzyme induction, place the population under selective pressure for degradation of recalcitrant substrates, and favor the simultaneous rather than sequential metabolism of a mixed carbon source.33 Carbon-limiting conditions can be achieved either through continuous culture (chemostat) or through a fed batch reaction. 

Figure 14.4 Gel image of proteins extracted from a mixed carbonic anhydrase lysozyme tissue surrogate. Lane M, molecular weight marker lane 1, a 1 2 mol ratio mixture of native, non-formalin-treated carbonic anhydrase and lysozyme lane 2, mixed surrogate with 1 2 mol ratio carbonic anhydrase lysozyme, solubilized and retrieved in 20mM Tris-HCl, pH 4.0, with 2% SDS lane 3, mixed surrogate with 1 2 mol ratio carbonic anhydrase lysozyme, solubilized and retrieved in 20mM Tris-HCl, pH 6.0, with 2% SDS. Protein bands corresponding to lysozyme monomer (a), carbonic anhydrase monomer (b), and the putative lysozyme-carbonic anhydrase heterodimer (c) are indicated. For more detail, see Reference 25.

The mixed carbonic anhydride procedure8-7 has been useful in the preparation of amide linkages and thiol esters. Mixed carbonic anhydrides have successfully acylated, under very mild conditions, the carb-anions derived from diethyl ethylmalonate and diethylcadmium.8 The latter gives as a product the corresponding ketone. Mixed anhydrides derived from acetic and acetylsalicylic acids give results similar to those described here.8... 

GW Anderson, JE Zimmerman, FM Callahan. A reinvestigation of the mixed carbonic anhydride method of peptide synthesis. J Am Chem Soc 89, 5012, 1967. 

JR Vaughan, RL Osato. The preparation of peptides using mixed carbonic-carboxylic acid anhydrides. J Am Chem Soc 74, 676, 1952. 

J Meienhofer. The mixed carbonic anhydride method of peptide synthesis, in E Gross, J Meienhofer, eds. The Peptides Analysis, Synthesis, Biology, Academic, New York, 1979, Vol 1, pp 263-314. 

FIGURE 2.27 More on additives. In a carbodiimide-mediated reaction between acid 1 and amine 2, addition of HOObt can lead to the side reaction of aminolysis at the carbonyl of the activating moiety of ester 3, generating addition product 4. Addition of HOBt to a mixed-anhydride reaction containing unconsumed chloroformate generates mixed carbonate 5, leading to production of urethane 6. 

There is a claim that HOBt suppresses undesired aminolysis at the carbonate carbonyl of a mixed anhydride (Figure 2.25, path F). It is rarely used for this purpose, but if it is, it must be added only after the chloroformate has been consumed otherwise, mixed carbonate 5 is formed, and it depletes the amino-containing component by acylating it, giving stable urethane 6 (Figure 2.27).2 UI 3477... 

FIGURE 3.15 Protection of amino groups as urethanes by reaction with succinimido carbonates (path A).33-36 The mixed carbonate is a weaker electrophile than the chloroformate. The V-alkoxycarbonylamino-acid anion does not react with the reagent (path B) in the presence of the weak base hence no dimer is formed. R = triethyl or dicyclohexyl. 

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