Carbon framework

Early investigators grouped alkaloids according to the plant families in which they are found, the stmctural types based on their carbon framework, or their principal heterocycHc nuclei. However, as it became clear that the alkaloids, as secondary metaboUtes (30—32), were derived from compounds of primary metabohsm (eg, amino acids or carbohydrates), biogenetic hypotheses evolved to link the more elaborate skeletons of alkaloids with their simpler proposed pregenitors (33). These hypotheses continue to serve as valuable organizational tools (7,34,35). 

This C2Q pyrophosphate (122), thought to provide the carbon framework of the diterpene alkaloids such as veatchine (123), atisine (124),... 

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). 

Hoffmaim-La Roche has produced -carotene since the 1950s and has rehed on core knowledge of vitamin A chemistry for the synthesis of this target. In this approach, a five-carbon homologation of vitamin A aldehyde (19) is accompHshed by successive acetalizations and enol ether condensations to prepare the aldehyde (46). Metal acetyUde coupling with two molecules of aldehyde (46) completes constmction of the C q carbon framework. Selective reduction of the internal triple bond of (47) is followed by dehydration and thermal isomerization to yield -carotene (21) (Fig. 10). 

The benzene ring has a fully symmetrical (Deh) planar hexagonal carbon framework. Heteroatom substitution upsets this symmetry, but except in certain special cases, as for instance the thiabenzenes , the planarity of the ring is preserved. Although it is known... 

Fig. 9.3. (A) Carbon framework from X-ray crystal stmcture of iyn-tricyclo[8.4.1.1]hexadeca-1,3,5,7,9,11,13-heptaene. (B) Side view showing deviation from planarity of aimulene ring. (Reproduced from Ref 60 by permission from the International Union of Crystallography.)...

CDP840 is a selective inhibitor of the PDE-IV isoenzyme and interest in the compound arises from its potential application as an antiasthmatic agent. Chemists at Merck Co. used the asymmetric epoxidation reaction to set the stereochemistry of the carbon framework and subsequently removed the newly established C-O bonds." Epoxidation of the trisubstituted olefin 51 provided the desired epoxide in 89% ee and in 58% yield. Reduction of both C-O bonds was then accomplished to provide CDP840. 

Construction of the carbon frameworks by using the activating property of the nitro group followed by denitration provides a useful tool for the preparation of various naniral products as shovm in Schemes 3 5-3 7 For example, fZ -jasmone and dihydrojasmone, constinients of the essential oilof jasmone flowers, have been prepared as shown in Scheme 3 5 Schemes 3 6 and 3 7 present a synthesis of pheromones via denitration of ct-nitro ketones " ... 

Now that the allylic oxidation problem has been solved adequately, the next task includes the introduction of the epoxide at C-l and C-2. When a solution of 31 and pyridinium para-tolu-enesulfonate in chlorobenzene is heated to 135°C, the anomeric methoxy group at C-l 1 is eliminated to give intermediate 9 in 80% yield. After some careful experimentation, it was found that epoxy ketone 7 forms smoothly when enone 9 is treated with triphenyl-methyl hydroperoxide and benzyltrimethylammonium isopropoxide (see Scheme 4). In this reaction, the bulky oxidant adds across the more accessible convex face of the carbon framework defined by rings A, E, and F, and leads to the formation of 7 as the only stereoisomer in a yield of 72%. 

The dihedral angles between the base plane (C 2, C 3, C 6, C 7) and the bow (S, C 2, C 7) plane (a) and stern (C3, C4, C5, C6) plane (/ ) of (bcnzo)thiepins are between 44.6-58.6 and 22.8-40.8, respectively, with the most pronounced bending being observed for 3,5-dimethoxy-4-phenyl-l-benzothiepin 1-oxide (Table 4).26 For thiepins, and their 1-oxides and 1,1-dioxides, the single and double bond alternation is obvious in the carbon framework. 

The FMO of the diene having substituent X at the 5-positions is comprised of three molecular orbitals, namely, jt-HOMO of the diene part, a-orbital of carbon framework, and the nonbonding (n) orbital of X (Scheme 3). The FMO of the diene for Diels-Alder reactions should mainly consist of n-HOMO. The jt-HOMO is antisymmetric with respect to reflection in the plane containing C5 carbon and its substitu-... 

As another example, the tropylium ion [3 ], which is stabilized by virtue of the 67t electrons spread over a heptagonal sp hybridized carbon framework [Hiickel s (4n 4- 2)v rule with = 1], is also unstable in the gas phase. Its formation from toluene or the benzyl cation has been a long-standing problem in organic mass spectrometry, and the reaction mechanism and energetics have recently been exhaustively discussed (Lif-shitz, 1994). It was, however, isolated as the bromide salt by Doering and Knox (1954, 1957), and was the first non-benzenoid aromatic carbocation. 

Kuhn s carbanion, the all-hydrocarbon anion tris(7//-dibenzo[c,g]-fluorenylidenemethyl)methanide ion [2 ] (Kuhn and Rewicki, 1967a,b), is a stabilized system with tt electrons widely spread over the sp hybridized carbon framework, and was isolated as the potassium salt. It also appears in DMSO solution by dissolving the parent hydrocarbon, resulting in a deep green colour. The pKg value of the precursor hydrocarbon [2]-H is 5.9 in aqueous HCl-DMSO (Kuhn and Rewicki, 1967a,b), and its enormous stability, as compared with cyclopentadiene [9]-H, pKa 18 in DMSO... 

One of the major organizing principles in organic chemistry is the presence of special arrangements of atoms. These so-called functional groups convey particular chemical properties. For example, a substance that contains an —OH group is called an alcohol. The systematic name of an alcohol is obtained by adding the suffix -ol to the name of the alkane with the same carbon framework. Thus, CH3 OH has the carbon framework of methane and is called methanol, whereas C2 H5 OH has the carbon framework of efhane and is called ethanol. 

The NMR techniques discussed so far provide information about proton-proton interactions (e.g., COSY, NOESY, SECSY, 2D y-resolved), or they allow the correlation of protons with carbons or other hetero atoms (e.g., hetero COSY, COLOC, hetero /resolved). The resulting information is very useful for structure elucidation, but it does not reveal the carbon framework of the organic molecule directly. One interesting 2D NMR experiment, INADEQUATE (Incredible Natural Abundance Double Quantum Transfer Experiment), allows the entire carbon skeleton to be deduced directly via the measurement of C- C couplings. 

The HMQC spectrum, H-NMR chemical shift assignments, and C-NMR data of vasicinone are shown. Consider the homonuclear correlations obtained from the COSY spectrum in Problem 5.14, and then determine the carbon framework of the spin systems. 

The 2D INADEQUATE spectrum provides carbon-carbon connectivity information and allows the entire carbon framework to be built up. The best strategy for the interpretation of a complex INADEQUATE spectrum is to start with the most downfield satellite carbon resonance and to trace the subsequent connectivities. Using this strategy,... 

The most common site for metalation of the carbon framework is C5 of the pyrimidines, C and U. For these reactions to occur, basic reaction conditions are generally required to assist in a deprotonation step. The first structurally characterized species was the di-Pt111 complex of 1-methyluracil, which also featured N3- and 04-binding (Pt-C5 distance... 

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