Have a look at the structures (a) and (b). They are the stereoisomers of laballenic acid, with (a) is naturally occurring in plants of the Lamiaceae family. What kind of stereoisomers are they?
-laballenic_acid.png) |
-laballenic_acid.png) |
| (a) | (b) |
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If there was just one double bond in the middle of the molecule, we’ll be dealing with cis/trans isomerism. But we have two cumulative double bonds, which makes our molecules chiral, even though there are no chiral atoms. Why?
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| (c) |
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The diagram (c) represents a generic allene structure. The central carbon atom has linear geometry (L-2); it is linked by double bonds to the trigonal planar (TP-3) carbon atoms. The whole structure, however, could be thought of as an elongated tetrahedron with vertices R1, R2, R3 and R4. Structures like that are said to have axial chirality. For an allene to be chiral (that is, not superposable on its mirror image), there’s no need to have four different substituents: that R1 ≠ R2 and R3 ≠ R4 will suffice. In (c), the chirality axis goes along the C=C=C bonds and the planes C(R1)(R2) and C(R3)(R4) are at 90° to each other. So (a) and (b) are enantiomers.
To specify the configuration of the molecules with axial chirality, the stereodescriptors ‘Ra’ and ‘Sa’ or ‘M’ and ‘P’ are used, with the latter convention being preferred by IUPAC [1, P-93.4.2.2]. We assign the priorities within each pair of substituents, viz. (R1, R2) and (R3, R4), according to the Cahn–Ingold–Prelog (CIP) sequence rules. As a result, we’ll have two axes, let’s call them ①–② and ①′–②′. If we look at the molecule along the chirality axis, we’ll see ①–② perpendicular to ①′–②′. Now we can use either of two methods:
- P/M convention [1, P-92.1.2.2.1]: if the sequence ①–①′ (or ①′–①, it doesn’t matter from which end you look) goes clockwise, it’s denoted by the ‘P’ (“plus”) stereodescriptor; if ①–①′ goes anticlockwise, it gets ‘M’ (“minus”).
- Ra/Sa convention [1, P-92.1.2.1.2]: if the sequence ①–②–①′ (or ①′–②′–①) goes clockwise, it’s ‘Ra’ (that is, “axial” R); otherwise — i.e. anticlockwise — it’s ‘Sa’ (“axial” S)*.
As you can see, ‘Ra’ corresponds to ‘M’ and ‘Sa’ to ‘P’. Therefore, we name (a) as either (5M)-octadeca-5,6-dienoic acid (PIN) or (5Ra)-octadeca-5,6-dienoic acid, and (b) (5P)-octadeca-5,6-dienoic acid (PIN) or (5Sa)-octadeca-5,6-dienoic acid.
One of the advantages of M/P system over the Ra/Sa can be demonstrated on the example of grasshopper ketone (d)†. In its systematic name, (3M)-4-[(2R,4S)-2,4-dihydroxy-2,6,6-trimethylcyclohexylidene]but-3-en-2-one, the stereodescriptor ‘M’ is easily distinguishable from the “real tetrahedral” descriptors ‘R’ and ‘S’.
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| (d) |
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Apart from molecules with an even number of cumulative double bonds [1, P-93.4.2.2], there are other classes of compounds that show axial chirality. Among them, hindered biaryls [1, P-93.5.7.1], which exhibit a type of isomerism know as atropisomerism. The Gold Book defines atropisomers as “subclass of conformers which can be isolated as separate chemical species and which arise from restricted rotation about a single bond”. For instance, (e) and (f) are atropisomers of 1,1′-bi-2-naphthol that result from rotation about the single bond connecting the two 2-naphthol moieties. This bond lies on the chirality axis. The structure (e) is a mirror image of (f), so the pair are atropoenantiomers.
-BINOL.svg) |
-BINOL.svg) |
| (e) | (f) |
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Applying the CIP sequence rules, we assign the priorities to the naphthalene ring atoms directly connected to the atoms C-1 and C-1′ of 1,1′-bi-2-naphthol. Since oxygen is senior to carbon, C(O,C,C) > C(C,C,C), so C-2 has priority ① and C-8a has priority ②. Once again, we have two axes, ①–② and ①′–②′, perpendicular to the chirality axis and to each other. Employing the methods described above, we can name the structure (e) (1P)-[1,1′-binaphthalene]-2,2′-diol (PIN) or (1Sa)-[1,1′-binaphthalene]-2,2′-diol, and its enantiomer (f) (1M)-[1,1′-binaphthalene]-2,2′-diol (PIN) or (1Ra)-[1,1′-binaphthalene]-2,2′-diol.
In axially chiral biaryl natural products there is marked preference of one atropisomer over the other. For example, the antibacterial and cytotoxic compound viriditoxin was isolated from several species of fungi, mostly as (M) atropisomer (g), with trace amounts of (P) atropisomer (h) [4].
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| (g) | (h) |
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Note that in addition to the chirality axis (collinear with the C-6—C-6′ bond), viriditoxin has two chiral atoms (C-3 and C-3′). The structures (g) and (h) are not enantiomers but atropodiastereomers.
| * | It is not clear how the descriptors ‘Ra’ and ‘Sa’ are supposed to be pronounced. “R axial” and “S axial” sound more Spanish than English because the adjective “axial” follows the descriptor. On the other hand, I saw the descriptors ‘aR’ and ‘aS’ used in Spanish chemical literature [2, p. 125]. Do the Spanish speakers pronounce them English way, that is, “axial R” and “axial S”? Go figure. (Cf. planar chirality descriptors ‘Rp’ and ‘Sp’.) |
| † | So called because it was first isolated from the grasshopper, Romalea microptera [3] but later found in other organisms such as algae and higher plants. |
References
- Favre, H.A. and Powell, W.H. Nomenclature of Organic Chemistry: IUPAC Recommendations 2013 and Preferred IUPAC Names. Royal Society of Chemistry, Cambridge, 2014.
- Quiroga Feijóo, M.L. Estereoquímica: conceptos y aplicaciones en química orgánica. Editorial Síntesis, Madrid, 2007.
- Meinwald, J., Erickson, K., Hartshorn, M., Meinwald, Y.C. and Eisner, T. (1968) Defensive mechanisms of arthropods. XXIII. An allenic sesquiterpenoid from the grasshopper Romalea microptera. Tetrahedron Letters 9, 2959—2962.
- Hu, J., Li, H. and Chooi, Y.-H. (2019) Fungal dirigent protein controls the stereoselectivity of multicopper oxidase-catalyzed phenol coupling in viriditoxin biosynthesis. Journal of the American Chemical Society 141, 8068—8072.
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