cyclo {[(6-Amino-6-deoxy-2,3:4,5-di-O -isopropyl- idene-D -galactonic acid)-( D -Phe)] 2 }

Determination of the crystal structure of the title compound [systematic name: 9,25-dibenzyl-4,4,15,15,20,20,31,31-octa­methyl-3,5,14,16,19,21,30,32-octa­oxa-8,11,24,27-tetra­aza­penta­cyclo­[27.3.0.02,6.013,17.018,22]dotriacontane-7,10,23,26-tetrone], C42H56N4O12, a cyclic tetra­mer, established the relative stereochemistry of its ten stereogenic C atoms; an inter­esting saddle-like conformation is adopted. There are two mol­ecules in the asymmetric unit. With the exception of the phenyl and isopropyl­idene groups, the mol­ecules are related by a non-crystallographic twofold rotation axis. There are varying degrees of disorder in the isopropyl­idene groups.


Comment
Carbohydrates which contain amine and acid groups are commonly referred to as sugar amino acids (SAAs) (Chakraborty et al., 2004;Gruner et al., 2002;Smith & Fleet, 1999). They have been the focus of much interest as dipeptide isosteres and library scaffolds, and their linear oligomers as foldamers (Jensen & Brask, 2005, Trabocchi et al., 2005. SAAs and -amino acids have been combined in cyclic peptides (Stockle et al., 2002;van Well et al., 2000) to create mimics of biologically active cyclic peptides (van Well, Over-

Figure 1
The title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radii. The bonds in the 20-membered ring are black. kleeft et al., 2003;Gruner et al., 2001). Several cyclic homooligomers have now been prepared using oxetane, furanose and pyranose SAAs (Johnson et al., 2006;van Well, Marinelli et al., 2003;Chakraborty et al., 2003); a cyclic hexamer of pyranose SAAs was found to form inclusion complexes akin to those of cyclodextrins (Locardi et al., 2001). A new family of cyclic SAA oligomers, based on acyclic SAAs, has been established (Mayes, Stetz et al., 2004;Mayes, Simon et al., 2004;Mayes, Cowley et al., 2004) and a cyclic dimer of galactose stereochemistry found to interact with probe compounds (Edwards et al., 2005). This family has now been expanded to include heterooligomers which incorporate phenylalanine (Phe).
The X-ray crystal structure confirms the structural integrity of the title compound, (3), and the absolute stereochemistry is determined by the use of d-galactonolactone as the starting material for the synthesis of (1). The saddle-like conformation adopted by (3) is of particular interest (Fig. 1).
The material crystallizes in P1, with two molecules in the asymmetric unit (Fig. 2). The ring atoms in both molecules adopt the same conformation, the only differences being in the phenyl groups, which adopt different conformations in each molecule. The methyl groups on the isopropylidene rings show elongated displacement ellipsoids, and as such are probably disordered. Only two of the eight groups, one on each ring, are actually disordered enough to be modelled as such. The remaining groups were best modelled by large ADP. One of the isopropylidene rings also shows a disordered O atom, suggesting that it is the O atom on the ring, rather than the C atom with the methyl groups attached, that is flipping. Indeed, the dimethyl C atom has a small, well shaped displacement ellipsoid, suggesting that it does not move to any great degree, and the ring flips about it.
When the phenyl groups, the hydrogen and the isopropylidene methyl groups are removed, it is found that the skeletons of the two rings map on to each other, related by a pseudo-twofold rotation axis (r.m.s. deviation in atomic position = 0.137 Å ; r.m.s. deviation in bond length = 0.012 Å ; r.m.s. deviation in torsion angles = 5.78 ).
The structure consists of ribbons of hydrogen-bonded molecules, with alternating inter-and intramolecular hydrogen bonds, parallel to the a axis (Table 1,

Experimental
Compound (3) was prepared by hydrogenation of the pentafluorophenyl ester of the linear SAA-Phe dimer (2) with palladized carbon in dioxane; no cyclic dimer was observed. The linear dimer (2) was prepared by coupling of the free acid of SAA (1) (Long et al., 1999) with the methyl ester of d-phenylalanine using standard peptide coupling reagents (O-benzotriazol-1-yl-N,N,N 0 ,N 0 -tetramethyluronium tetrafluoroborate and triethylamine). The sample for X-ray analysis was crystallized from methanol.  The asymmetric unit, viewed parallel to a, with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radii.

Figure 3
Packing diagram, viewed along the a axis, showing the hydrogen-bonded ribbons end on.  Table 1 Hydrogen-bond geometry (Å , ). In the absence of significant anomalous scattering, Friedel pairs were merged. To model the disorder, those atoms with unusually elongated displacement ellipsoids were split, and each atom given an occupancy of 0.5. Coordinates, U ij values and site occupancies of these atoms were then refined. No geometric restraints were applied. The isopropylidene ring containing C56-C59 showed significant deviation from equal occupancies, ending up at 0.581 (4):0.419 (4).
The isopropylidene ring containing C144-C157 showed no deviation from equal occupancies, with the occupancies converging to 0.500 (3):0.500 (3). The H atoms were all located in a difference map, but those attached to C atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C-H in the range 0.93-0.98 Å , N-H in the range 0.86-0.89 Å and O-H = 0.82 Å ) and displacement parameters [U iso (H) in the range 1.2-1.5 times U eq of the parent atom], after which they were refined with riding constraints.