Prenol Nomenclature Recommendations 1986

Eur. J. Biochem. 167,181 -184 (1987) 0 FEBS 1987 EJB - 870270

IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN) Prenol nomenclature Recommendations 1986

CONTENTS The carbon atoms along the main chain are numbered Introduction ...... 181 from C-1, the atom that carries the hydroxyl group (C-15.11 General terms ...... 181 of ref. 8). The methyl group carried by atom C-3 contains Pr-1. Prenol...... 181 atom C-3l, that carried by atom C-7 contains atom C-7l, etc. Pr-2. Polyprenol ...... 181 Pr-3. Esters and their derivatives . . 181 Note Pr-4. Number of residues ...... 181 Stereochemistry ...... 181 This use of superscript numbers is based on section TP-2.1 Pr-5. Double bonds...... 181 of the recommendations for the nomenclature of tetrapyrroles Pr-6. Order of stereochemical prefixes...... 182 [9]. In the printing of these recommendations in the European Pr-7. Multiplicative prefixes ...... 182 Journal of Biochemistry the relevant paragraph was acci- Spec fie compounds ...... 182 dentally transposed to the caption of Table 2. Pr-8. Trivial names ...... 182 The repeating CsHs unit (inside the brackets of structure Pr-9. Isopentenyl diphosphate ...... 184 Pr-10. Relationship between polyprenols and isoprenoids 184 Z) is termed an isoprene unit or an isoprene residue. Prenols Pr-1 1. Juvenile hormones ...... 184 and their esters are precursors of a variety of compounds, Pr-12. Dolichols ...... 184 including terpenes and steroids, that have much of the carbon References ...... 184 skeleton intact. Such compounds are known as isoprenoids.

INTRODUCTION Pr-2. Polyprenol. Polyprenols represent a subgroup of prenols. The term polyprenol, already widely used (e. g. ref. 2), is Present practice in the nomenclature of prenols takes little recommended for compounds of structure Z in which n is account of the important stereochemistry of these greater than 4. compounds. We therefore believe that a review of existing practice, with recommendations for specifing stereochemistry, Pr-3. Esters and their derivatives. The terms prenyl should be helpful. Some of the recommendations have been diphosphate (or diphosphoprenol) and polyprenyl diphos- used in Enzyme nomenclature [l]. phate (or diphosphopolyprenol), already widely used, are recommended for the esters of Z with diphosphoric acid, and GENERAL TERMS for the salts and anions of such esters. They are in accordance with recommendations for naming phosphorus-containing Pr-1. Prenol. The term prenol, already widely used (e. g. compounds [7]. refs 2,3,5,6), is recommended to describe the structure shown in formula I. It originated as a contracted name for isoprenoid alcohol (i.e. suffix -01) [2]. Note The term prenyl diphosphate is preferred to diphosphoprenol, because diphosphate has precedence over hydroxyl Z for being cited as suffix (C-10.3 of ref. 8). Pr-4. Number of residues. The number of isoprene residues, This is a document of the IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN), whose members are H.B.F. i.e. the value of n in Formula Z, in each molecule of a Dixon (Chairman), A. Cornish-Bowden (Secretary), C. Likbecq (re- polyprenol or derivative should be indicated by a presenting the IUB Committee of Editors of Biochemical Journals), multiplicative prefix [lo] instead of the general prefix poly- K.L. Loening, G.P. Moss, J. Reedijk, P. Venetianer and J.F.G. suggested in recommendation Pr-2, e. g. hexaprenol, hepta- Vliegenthart. Comments may be sent to any member of the commis- prenyl diphosphate. sion, or to its secretary: A. Cornish-Bowden, CNRS-CBM, 31 Chemin Joseph-Aiguier, F-13402 Marseille Cedex 9, France. JCBN thanks a panel whose members were W.L. Adair (USA), C.M. Allen (USA), STEREOCHEMISTRY T.W. Goodwin (UK), F.W. Hemming (UK, convenor), K. Ogura Pr-5. Double bonds. The double bond in a residue is called (Japan), J.F. Pennock (UK), T.W. Porter (USA), H.C. Rilling (USA) cis or trans according to whether the main chain of the com- and D.R. Threlfall (UK), for drafting these recommendations, and present, former and associate members of the Nomenclature pound is cis or trans across that double bond. A residue Committee of IUB (NC-IUB), namely C.R. Cantor, P. Karlson, N. containing a cis double bond may be called a cis residue, and Sharon, E.J. Van Lenten, S.F. Velick and E.C. Webb, for help in one containing a trans double bond may be called a trans preparing them. residue. 182

Note used, (2) it corresponds to the left-to-right order in most drawings of formuias and symbolic representations of prenols The designations cis and trans refer to the ‘Onfiguration of the main chain across a double bond. Thus, unlike Z and and their diphosphates, and (3) it first the double bonds formed first in biosynthesis. E [ll],they are independent of any substituents that may be present. This recommendation does not preclude the use of Z Example and E. all-trans-Nonaprenol is the plant product solanesol, which Pr-6. Order of stereochemicalprefixes. The residue furthest contains nine isoprene units, eight of which are trans, the from the hydroxyl group is referred to as the o-residue, and ninth being the o-residue. stereochemical designations are given in order from the residue next to the w-residue, endingwith the residue that carries Pr-7. Multiplicative prefixes. The prefix poly- may be re- the hydroxyl group, e. g. ditrans,polycis-undecaprenol(II). placed by an appropriate multiplicative prefix; e. g. the bac-

Notes terial product bactoprenol can be called ditrans,octacis- undecaprenol rather than ditrans,polycis-undecaprenol. 1. The distinction between cis and trans forms does not exist for the o-residue unless one of the two methyl groups is Note substituted. Therefore, stereochemical designators are given starting from the residue next to the o-residue. If this recommendation is followed it is not advisable to 2. It is not advisable to omit stereochemical designations, omit the multiplicative prefix indicating the total number of as this can give ambiguity. Thus the name heptaprenyl residues, even though it contains redundant information. In diphosphate was applied [12] to the all-trans compound from ditrans,octacis-undecaprenol,for example, a prenol with one a bacterium, but could be confused with ditransgolycis-hepta- w, two trans and eight cis residues must have eleven residues prenyl diphosphate, which is found in silver birch and other in all. plants [13]. The name undecaprenyl diphosphate was likewise applied [14] to the bacterial ditrans,polycis compound, which SPECIFIC COMPOUNDS could cause confusion with the tritrans,polycis compound found in the leaves of higher plants [15]. Pr-8. Trivial names. Several short-chain prenols are known 3. Although large numbers of stereoisomers could arise if by trivial names. For example, the diphosphates with one to each newly added residue (Fig. 1) could be either cis or trans, five residues are named as shown in Table 2. the commonest prenols are confined to four main groups Dimethylallyl diphosphate (strictly 3,3-dimethylallyl di- (Fig. 2), as follows: (i) all-trans-prenols, (ii) ditransgolycis- phosphate), geranyl diphosphate and neryl diphosphate are prenols, (iii) tritrans,polycis-prenols, and (iv) all-cis-prenols. Table 2 The symbols W, T and C that appear in Fig. 2, together with a fourth symbol S, provide a convenient set for representing Number Stereochemistry Trivial name polyprenol structures compactly as shown in Table 1. of residues

Table 1 1 (none) dimethylallyl diphosphate Symbol Meaning 2 tram geranyl diphosphate W w-residue cis neryl T trans-residue diphosphate C cis-residue 3 2-trans,6-trans S saturated (dihydro) residue 2-cis,6-trans farnesyl 2-trans,6-cis diphosphate 2-cis,6-cis In group (i), the term ‘all-trans’means that all the residues 4 2-trans,6-trans,lO-trans geran ylgeran yl except the o-residue have the trans configuration. In groups diphosphate 2-cis,-6-trans,lQ-trans geran ylneryl (ii) and (iii) the trans residues are grouped next to the o- diphosphate residue. Group (iv) is less well characterized, but probably exists as precursors of natural rubber. 5 2-trans,6-trans,lO-trans,l4-trans 4. The recommendation to cite stereochemical prefixes in 2-cis,6-trans,lO-trans,l4-trans geranylfarnesyl diphosphate the reverse order from their locants is contrary to normal 2-trans,6-cis,lO-trans,l4-trans 2-cis,6-cis,lO-trans,1Ctrans recommendations. We make it because (1) it is already widely J 183 CH3 0-POP CH3 0-POP CH3*? H CH3 0-POP I II I :I I I C / \ ,c\ A\ /CH2 R-CH2 R-CH2 C C 1 F\ I H H HH H HH*H Fig. 1. The chain-lengthening step in prenol biosynthesis entirely specified by name, and need no further stereochemical reverse order from that used for polyprenols (recommenda- designation. Dimethylallyl is the trivial name for 3-methylbut- tion Pr-6). We therefore recommend that locants should be 2-enyl. The name dimethylallyl does not conform to ref. 8, used to minimize confusion, e. g. 2-cis,6-trans-farnesyl diphos- and is ambiguous if used outside biochemical contexts. phate; this becomes trans,cis when lengthened to form the w- The name farnesyl diphosphate covers four CI5 terminus of a polyprenol. stereoisomers. It is confusing that they have been designated Two C20 prenyl groups have been named geranylgeranyl trans,trans, cis,trans, trans,cis and cis,cis, with the first de- and geranylneryl; in them the second isoprene residue from signator applying to C-2 and the second to C-6 [16], i.e. the the oxygen atom is always trans, i. e. the group is 6-trans. The

WTTTT, -POP all-trans-polyprenyl-POP Group (i) 1 1,30,33/ WTTT -POP geranylgeranyl-POP (all-trans) 1 1,29,30,33/\ WTT-POP WTTTC, -POP trans, trans-farnesyl-POP tritrans, polycis-polyprenyl-POP Group (ii) e.g. ficaprenyl-POP lo,ll/ \

WT-POP WTTC-POP geran yl-POP geranylneryl-POP (2-trans) (2-cis, 6. IO-ditrans)

1/\ WTC-POP WTTCC-POP / 2-cis, 6-trans-farnesyl-POP ditrans, polycis-polyprenyl-POP Group (iii) w-POP e.g. bactoprenyl-POP dimethylallyl-POP dehydrodolichyl-POP

wc-POP neryl-POP (2-cis)

WCC-POP cis, cis-farnesyl-POP

-%- wcccc,-PoP all-cis-polyprenyl-POP Group (iv) Fig. 2. Stereochemistry of polyprenol biosynthesis. Each arrow shows a transformation of the type given in Fig. 1. Upward sloping arrows represent trans additions of a unit from isopentenyl diphosphate (section Pr-9), and downward sloping arrows represent cis additions. An arabic numeral adjacent to an arrow indicates that an enzyme catalysing the reaction has been characterized and listed under that number in group EC 2.5.1 of Enzyme Nomenclature [l], e.g. EC 2.5.1.I 1 catalyses the conversion of geranyl-POP into trans,trans-farnesyl-POP.The groups given in the right-hand column refer to the main classes of polyprenols as listed in section Pr-6, note 3. Where locants are included the prefixes appear in locant order (section Pr-S), not in left-to-right order (section Pr-6). In the symbolic representation, W represents an o-residue, T a trans residue, and C a cis residue use of these terms is so widespread and well established that Examples it would probably be damaging to recommend changes. Other CHB-CHZ 7H3 compounds should be named according to sections Pr-4 to Pr- I 7, e. g. dicis,trans-tetraprenyl diphosphate for the compound with 2-trans-6,lO-dicis stereochemistry. ditrans-1 1 '-methylfarnesol Note We see no harm in using the polyprenol system (sections 7H3 CH3 -7HZ Pr-4 to Pr-7) for C20 compounds (i.e. naming them as tetraprenols). This usage eliminates the inconsistency of re- versing the order of stereochemical designators for com- ditrans-7' ,12-dimethylfarnesol pounds of fewer than five residues. Pr-9. Zsopentenyl diphosphate. An important isomer of Pr-12. Dolichol. Dolichols are a group of prenol dimethylallyl diphosphate is isopentenyl diphosphate derivatives. The term, already widely used (e. g. ref. 2), is rec- (structure ZZZ), the diphosphate of 3-methylbut-3-en-1-01 ommended for compounds of structure Z in which n is greater (isopentenyl alcohol). It is the universal building block of than 4 and in which the residue that carries the hydroxyl isoprenoids; a prenyl diphosphate reacts with it to lose group is saturated, i. e. 2,3-dihydropolyprenols. As dolichols diphosphate and grow longer by one residue (Figs 1 and 2). are derivatives of prenols the collective term prenol should Its name should be retained. not be used without qualification to include dolichols. 3' 7H3 I REFERENCES CH2 =C-CH*-CH2-O-P-O-P ZZl 4 32 I 1. Nomenclature Committee of the International Union of Bio- chemistry (1984) Enzyme nomenclature, 1984. Academic Press, Notes Orlando, Florida. 1. The CH2= group of isopentenyl alcohol contains C-4 2. Hemming, F. W. (1974) in Biochemistry, Series One, vol.4 [see recommendation C-13.11(b) of ref.81. This is convenient, (Goodwin, T. W., ed.) pp. 39-97, Buttenvorths, London. as C-4 of isopentenyl diphosphate is the precursor of C-4 of 3. IUPAC-IUB Commission on Biochemical Nomenclature (CBN). a lengthened prenol (Fig. 1). Nomenclature of quinones with isoprenoid side-chains. Re- commendations, 1973. Biochem. J. 147, 15-21 (1975); Eur. J. 2. The name isopentenyl is recommended only for bio- Biochem. 53, 15-18 (1975); Pure Appl. Chem. 38, 44-447 chemical use; it does not conform to ref. 8 and is ambiguous (1974); also pp. 154- 157 in ref.4. outside biochemical and prenol contexts. Isopentenyl is the 4. International Union of Biochemistry (1978) Biochemical trivial name for 3-methylbut-3-enyl. nomenclature and related documents, The Biochemical Society, London. Pr-10. Relationship between polyprenols and isoprenoids. 5. Popjbk, G. & Cornforth, J. W. (1960) Adv. Enzymol. 22, 281 - The derived isoprenoids are named as listed in Table 3. 335. 6. Holloway, P. W. & Popjbk, G. (1967) Biochem. J. 104, 57-68. Table 3 7. IUPAC-IUB Commission on Biochemical Nomenclature, Nomenclature of phosphorus-containing compounds of bio- Number Prenol precursor (as Terpenoid class chemical importance. Recommendations, 1976. Biochem. J. of diphosphate, etc.) 171, 1-19 (1978); Eur. J. Biochem. 79, 1-9 (1977); Hoppe- residues Seyler's Z. Physiol. Chem. 358, 599-616 (1977); Proc. Natl Acad. Sci. USA, 74, 2222-2230 (1977); also pp.203-211 in dimethylallyl alcohol hemiterpenoid ref.4. geraniol or nerol monoterpenoid 8. International Union of Pure and Applied Chemistry (1979) farnesol sesquiterpenoid Nomenclature of organic chemistry, Sections A, B, C, D, E. F geranylgeraniol diterpenoid and H (Rigaudy, J. & Klesney, S. P., eds), Pergamon Press, geranylfarnesol sesterterpenoid Oxford. farnesol" triterpenoid" 9. IUPAC-IUB Joint Commission on Biochemical Nomenclature. geranylgeraniol ' tetraterpenoid Nomenclature of tetrapyrroles. Recommendations, 1978. Eur. or carotenoid' J. Biochem. 108, 1-30 (1980); Pure Appl. Chem. 51, 2251- many rubber (all-cis) 2304 (1979). gutta percha (all-trans) 10. Sections A-I and A-2.5 of ref. 8, extended by IUPAC Commission on Nomenclature of Organic Chemistry (CNOC). Pure Appl. a Triterpenoids are formed from squalene, which is derived from Chem. 58, 1693-1696 (1986). two farnesyl diphosphate precursor molecules. 11. International Union of Pure and Applied Chemistry (1976) ' Carotenoids are formed from phytoene, which is derived from Stereochemistry, Pure Appl. Chem. 45, 11 -30 (1976); also pp. two geranylgeranyl diphosphate precursor molecules. 1 - 5 in ref. 4 and Section E of ref. 8. 12. Takahishi, I., Ogura, K. & Seto, S. (1980) J. Biol. Chem. 255, Pr-11. Juvenile hormones. Farnesol is the prenol that corre- 4539-4543. sponds to the carbon skeleton of the simplest juvenile 13. Wellburn, A. R. & Hemming, F. W. (1966) Nature (Lond.) 212, hormone. Other members of this group of compounds have 1364- 1366. 14. Allen, C. M., Keenan, M. V. & Sack, J. (1976) Arch. Biochem. an ethyl instead of a methyl group at C-3 and/or C-7 and/or Biophys. 175, 236-248. C-11. These may be specified as methyl-substituted farnesol 15. Wellburn, A. R., Stevenson, J., Hemming, F. W. & Morton, R. derivatives where the stereospecificity of the w-isoprene unit A. (1967) Biochem. J. 102, 313-3324, (where relevant) is indicated by which methyl group is sub- 16. Bates, R. B., Gale, D. M. & Gruner, B. J. (1963) J. Org. Chem. stituted. 28, 1086-1089.